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Article

Straightforward Synthetic Approach to Aminoalcohols with 9-oxabicyclo[3.3.1]nonane or Cyclooctane Core via Nucleophilic Ring-Opening of Spirocyclic Bis(oxiranes)

by
Olga V. Ryzhikova
,
Daiana V. Savchenkova
,
Sergey V. Kositov
,
Yuri K. Grishin
,
Olga A. Maloshitskaya
,
Kseniya N. Sedenkova
and
Elena B. Averina
*
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia
*
Author to whom correspondence should be addressed.
Molecules 2026, 31(2), 252; https://doi.org/10.3390/molecules31020252
Submission received: 16 December 2025 / Revised: 2 January 2026 / Accepted: 3 January 2026 / Published: 12 January 2026
(This article belongs to the Section Organic Chemistry)
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Abstract

Nucleophilic ring-opening of bis(oxiranes), containing several reactive centers, can be used to elaborate straightforward atom-economy and stereoselective approaches to polyfunctionalized compounds. In the present work, ring-opening of cis- and trans-diastereomers of a spirocyclic bis(oxirane), containing a cyclooctane core (namely, 1,8-dioxadispiro[2.3.2.3]dodecane), upon treatment with various amines, was studied. Trans-isomer afforded aminoalcohols with 9-oxabicyclo[3.3.1]nonane moiety, formed via domino-process, including opening of an oxirane ring followed by intramolecular cyclization. Ring-opening of cis-isomer gave aminosubstituted cis-cyclooctane-1,5-diols, derived from independent reaction of two oxirane moieties. Activation of oxirane rings by the addition of LiClO4, acting as a Lewis acid, allowed the involvement of a number of primary and secondary aliphatic amines as well as aniline derivatives in the reaction. Scope and limitations of the reaction were studied and a series of aminoalcohols with a 9-oxabicyclo[3.3.1]nonane core and symmetric diaminodiols with a cyclooctane core were obtained.

1. Introduction

Oxiranes represent versatile intermediates, finding application in the synthesis of medicinal drugs, natural compounds, polymers, and other products with practicable properties [1,2,3,4,5]. Synthetically useful transformations of these strained rings are characterized by predictability, regio- and stereoselectivity [6,7], mild conditions, and broad reaction scope [8,9,10,11,12]. Bis(oxiranes), containing several reactive centers, are structures of particular interest. Generally, they are used to elaborate straightforward approaches to polyfunctionalized compounds [13,14,15], though examples of formation of saturated O-heterocycles via intramolecular cyclization are reported as well [16,17]. An eight-membered ring present in the molecule opens additional synthetic opportunities due to transannular transformations leading to polycyclic structures [18,19].
Aminoalcohols and diaminodiols are of interest as scaffolds occurring in a number of bioactive and natural compounds (Figure 1). For instance, adrenalin represents a β-aminoalcohol, as well as a number of adrenergic drugs, such as a short-acting bronchodilator albuterol [20]. Linear aminodiol or aminopolyol moieties are present in natural antibiotics such as amicoumacin A [21] and zwittermicin A [22]. 2-Deoxystreptamine (2-DOS), containing a cyclohexane core, is of importance as a key aminocyclitol scaffold of a number of clinically used aminoglycoside antibiotics (gentamicin, neomycin, etc.) [23]. Conformationally constrained aminoalcohols, such as compound I, represent rigid peptidomimetics [24].
Previously, we have reported the first example of transannular reactions of spirocyclic bis(oxirane) trans-1 as a nucleophile (Scheme 1) [25], which was later expanded for a tetrakis(oxirane) [26]. The reactivity of two diastereomers of bis(oxirane) trans-1 and cis-1 towards NaN3 was investigated and it was shown to be determined by the configuration of oxirane moieties: while trans-1 afforded 9-oxabicyclo[3.3.1]nonane 2, formed via domino process, including opening of one oxirane ring followed by intramolecular cyclization, diastereomer cis-1 gave the sole isomer of diazidodiol 3, derived from independent ring-opening of two oxirane moieties.
It should be mentioned that molecules containing cleft-shaped frameworks such as bicyclo[3.3.1]nonanes and their aza-derivatives have found application as conformationally restricted molecules for the purposes of medicinal chemistry, metal complex catalysis, and the detection of metal ions and small molecules [27]. Natural and synthetic derivatives of aza- and diazabicyclo[3.3.1]nonanes (granisetron, pentazocine, cytisine) are used as medicinal drugs (Figure 2) [28,29,30]. Numerous natural compounds containing fragments of bicyclo[3.3.1]nonane (for example, polycyclic polyprenylated acylphloroglucinols (PPAPs) [31,32]), 2-azabicyclo[3.3.1]nonane (morphine alkaloids [33]), 9-azabicyclo[3.3.1]nonane (granate [34] and bis(indole) alkaloids [35]), 3,7-diazabicyclo[3.3.1]nonane (bispidine-based alkaloids [36]), as well as synthetic bicyclo[3.3.1]nonanes, reveal a broad spectrum of biological activity, including anticancer properties [37,38,39,40].
9-Oxabicyclo[3.3.1]nonane moiety, as well as similar frameworks, represents a conformationally restricted 3D-scaffold attractive for drug design and occurring in bioactive compound. For example, diterpenoid II (Figure 2) exhibits antiproliferative activity towards cancer cells with good selectivity compared to normal cell lines [41]. At the same time, in contrast to the above-mentioned bicyclononane derivatives, 9-oxabicyclo[3.3.1]nonanes are rather hard to synthesize and much less examples of them are described; that makes the search for straightforward approaches to these compounds a challenging task.
As for diazidodiol 3, it represents an attractive structure to be used as a linker moiety for construction of conjugates for biomedical applications using azide–alkyne cycloaddition strategies [42,43]. It was successfully used to obtain bis(triazoles) [44] and bis(steroid) derivatives with anticancer activity [45].
In the present work, we aimed to study the nucleophilic ring-opening of bis(oxiranes) trans-1 and cis-1 upon treatment with various amines in order to elaborate preparative approaches to aminoalcohols and diaminodiols of previously unknown structural types.

2. Results and Discussion

A diastereomeric mixture of bis(oxiranes) trans-1 and cis-1 was studied upon the treatment with n-butylamine, morpholine, azepane, and aniline (Scheme 2). The reactions were performed under reflux in the medium of an amine without a solvent. In the case of n-butylamine, 9-oxabicyclo[3.3.1]nonane 5a, derived from transannular reaction of trans-1, was the only product. Cis-bis(oxirane) did not interact with butylamine. Reaction of trans-1 and cis-1 with more nucleophilic morpholine and azepane besides oxabicyclononane derivatives 5b,c afforded symmetric diaminodiols 6b,c, the products of independent ring-opening. Diaminodiols 6b,c were obtained as diastereomeric mixtures where cis-isomers prevailed. The configuration of isomers 6b,c was established based on different symmetries of molecules as previously performed for the starting bis(oxiranes) [25]. Aniline did not interact with bis(oxiranes) trans-1 and cis-1 in these conditions. The obtained preliminary results were in good correlation with the nucleophilicity of amines: secondary amines interacted with both trans-1 and cis-1; less nucleophilic butylamine interacted only with trans-1, able to undergo quick intramolecular reaction; the least nucleophilic aniline reacted with neither of the diastereomers.
In order to involve a broader scope of amines into the reaction and to improve its yield and selectivity, the conditions of nucleophilic opening were optimized on the examples of morpholine and butylamine. The solvent, temperature, time, and reagent ratios were varied (see Table S1). In the absence of basic or acidic additives, the reaction proceeded slowly even in acetonitrile under reflux, and an attempt to employ K2CO3 as a base led to complete decomposition of organic material. The use of LiClO4, chosen because of its ability to promote oxiranes’ ring-opening by acting as Lewis acid with non-nucleophilic anion [46], provided almost complete conversion of trans-1 and cis-1 at room temperature, though it required three days in the case of morpholine. Optimal reaction conditions were found to be reflux in acetonitrile for 5 h. Various quantities of LiClO4 were required, depending on the structure of amine: reactions with butylamine required 10-fold excess per oxirane ring, while for more nucleophilic morpholine, 1.2-fold excess per oxirane ring was enough for the complete conversion of starting bis(oxiranes). It should be mentioned that in optimized conditions, only cis-isomers of diaminodiols 6 were formed, i.e., only transannular reaction proceeded for trans-1a.
Bis(oxiranes) trans-1 and cis-1 were treated with various amines under optimized conditions (Table 1). In most cases, the diastereomeric mixture of starting bis(oxiranes) was involved into the reaction, with the ratio of starting diastereomers trans-1:cis-1 varying from 1:0.8 to 1:0.9; in some cases, when the products were hard to separate, either pure trans-1 or cis-1 was used as the starting material. Bis(oxirane) trans-1 smoothly reacted with primary and secondary amines, affording aminoalcohols 5a–k of 9-oxabicyclo[3.3.1]nonane series. Aniline, as well as EDG-substituted p-toluidine and p-anisidine, afforded the products of transannular reaction 5l–n after reflux for 5–10 h, while the reaction with p-bromoaniline gave the product 5o only after reflux for 30 h. Bis(oxirane) cis-1 also interacted with aliphatic and aromatic amines; yet, unfortunately, the resulting diaminodiols 6 were hard to isolate due to low chromatographic mobility and the tendency to form salts. Nevertheless, diaminodiols 6a–f could be isolated via column chromatography in moderate to high yields. Reaction of cis-1 with p-bromoaniline even after 40 h afforded an equimolar mixture of diaminodiol 6o and 7-{[(4-bromophenyl)amino]methyl}-1-oxaspiro[2.7]decan-7-ol (7o), which was the product of ring-opening of one oxirane moiety. Amines with stronger electron-acceptor substituents, namely, p-nitroaniline, sulfanilamide, and methanesulfonamide, did not act as nucleophiles towards bis(oxiranes) trans-1 and cis-1 in the described conditions.
To summarize, a preparative method of ring-opening of spirocyclic bis(oxiranes) trans-1 and cis-1 upon treatment with various amines in the presence of LiClO4 was elaborated to yield a series of aminoalcohols with 9-oxabicyclo[3.3.1]nonane core and substituted cis-cyclooctane-1,5-diols, containing two fragments of amine. The products of the ring-opening of bis(oxirane) trans-1, functionalized 9-oxabicyclo[3.3.1]nonanes, represent a valuable conformationally restricted scaffold for drug design, while the ring-opening of bis(oxirane) cis-1 with bioactive amines may be used as a stereoselective approach to bivalent ligands with a hydrophobic linker.

3. Materials and Methods

3.1. General

1H and 13C NMR spectra were recorded on a 400 MHz spectrometer Agilent 400-MR (Agilent Technologies, Santa Clara, CA, USA; 400.0, 100.6 or 376.3 MHz for 1H, 13C or 19F, respectively) at r.t. in CDCl3, if not stated otherwise; chemical shifts δ were measured with reference to CDCl3 (δH = 7.26 ppm, δC = 77.16 ppm) or to CFCl3. When necessary, assignments of signals in NMR spectra were made using 2D techniques. Accurate mass measurements (HRMS) were obtained on Bruker micrOTOF II (Bruker Daltonik GmbH, Bremen, Germany) or G3 QTof quadrupole-time-of-flight (Waters, Milford, MA, USA) with electrospray ionization (ESI). Analytical thin layer chromatography was carried out with silica gel plates supported on aluminum (ALUGRAM® Xtra SIL G/UV254, Macherey-Nagel, Duren, Germany); the detection was performed by UV lamp (254 nm). Column chromatography was performed on silica gel (Silica 60, 0.015–0.04 mm, Macherey-Nagel, Duren, Germany). Bis(oxiranes) trans-1 and cis-1 [25] were obtained via the described method. All other starting materials were commercially available. All reagents except commercial products of satisfactory quality were purified according to literature procedures prior to use.

3.2. Reaction of Bis(oxiranes) trans-1 and cis-1 with Amines (General Method)

To a solution of bis(oxirane) (0.1 mmol, 17 mg) in dry CH3CN (3 mL), LiClO4 (0.5–2 mmol) and corresponding amine (0.22 mmol) were added. The mixture was stirred at 80 °C for 5–40 h. The solvent was evaporated under reduced pressure. The product was isolated via preparative column chromatography (SiO2).
{5-[(Butylamino)methyl]-9-oxabicyclo[3.3.1]nonan-1-yl}methanol (5a). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 81% (20 mg), yellow oil, Rf 0.20 (light petrol:EtOAc:MeOH 3:1:0.1). 1H NMR (δ, ppm, J, Hz): 0.91 (t, 3H, 3J = 7.3, CH3), 1.27–1.39 (m, 4H, 2CH2, cy-Oct + CH2, Bu), 1.39–1.57 (m, 4H, 2CH2, cy-Oct + CH2, Bu), 1.58–1.75 (m, 6H, 6CH2, cy-Oct), 1.91–2.08 (m, 2H, 2CH2, cy-Oct), 2.54 (s, 2H, CH2N), 2.61–2.69 (m, 2H, CH2N, Bu), 3.11 (br.s, 2H, OH + NH), 3.31 (s, 2H, CH2OH). 13C NMR (δ, ppm): 14.1 (CH3), 18.5 (2CH2, cy-Oct), 20.6 (CH2, Bu), 29.8 (2CH2, cy-Oct), 31.4 (CH2, Bu), 31.8 (2CH2, cy-Oct), 50.2 (CH2N, Bu), 61.2 (CH2N), 71.4 (CH2OH), 71.7 (C-CH2N), 72.5 (C-CH2O). HRMS (ESI+, m/z): calculated for C14H27NO2 [M + H]+: 242.2115, found: 242.2122.
[5-(Morpholin-4-ylmethyl)-9-oxabicyclo[3.3.1]nonan-1-yl]methanol (5b). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:5. Yield 88% (22 mg), orange oil, Rf 0.20 (light petrol:EtOAc:MeOH 3:1:0.1). 1H NMR (δ, ppm): 1.28–1.46 (m, 4H, 4CH2, cy-Oct), 1.57–1.78 (m, 6H, 6CH2, cy-Oct), 1.94–2.11 (m, 2H, 2CH2, cy-Oct), 2.23 (s, 2H, CH2N), 2.37 (br.s, 1H, OH), 2.51–2.62 (m, 4H, 2CH2N, morpholine), 3.28 (s, 2H, CH2OH), 3.64–3.73 (m, 4H, 2CH2O, morpholine). 13C NMR (δ, ppm): 18.8 (2CH2, cy-Oct), 29.8 (2CH2, cy-Oct), 31.9 (2CH2, cy-Oct), 55.7 (2CH2N, morpholine), 67.2 (2CH2O, morpholine), 70.0 (CH2N), 71.6 (CH2OH), 72.1 (C-CH2O), 73.7 (C-CH2N). HRMS (ESI+, m/z): calculated for C14H25NO3 [M + H]+: 256.1907, found: 256.1906.
[5-(Azepan-1-ylmethyl)-9-oxabicyclo[3.3.1]nonan-1-yl]methanol (5c). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:5. Yield 54% (15 mg), yellow oil, Rf 0.26 (light petrol:DCM:MeOH 1:3:1). 1H NMR (δ, ppm): 1.31–1.47 (m, 4H, 4CH2, cy-Oct), 1.51–1.73 (m, 14H, 6CH2, cy-Oct + 4CH2, azepane), 1.93–2.09 (m, 2H, 2CH2, cy-Oct), 2.41 (s, 2H, CH2N), 2.73–2.83 (m, 4H, 2CH2N, azepane), 3.29 (s, 2H, CH2OH), 4.62 (br.s, 1H, OH). 13C NMR (δ, ppm): 18.9 (2CH2, cy-Oct), 27.5 (2CH2, azepane), 29.1 (2CH2, azepane), 30.0 (2CH2, cy-Oct), 31.7 (2CH2, cy-Oct), 57.9 (2CH2N, azepane), 69.2 (CH2N), 71.79 (CH2OH), 71.83 (C-CH2OH), 74.4 (C-CH2N). HRMS (ESI+, m/z): calculated for C16H29NO2 [M + H]+: 268.2271, found: 268.2272.
[5-(Piperidin-1-ylmethyl)-9-oxabicyclo[3.3.1]nonan-1-yl]methanol (5d). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:5. Yield 78% (13 mg), yellow oil, Rf 0.14 (light petrol: DCM:MeOH 1:3:0.5). 1H NMR (δ, ppm): 1.29–1.48 (m, 4H, 4CH2, cy-Oct + 2H, CH2, piperidine), 1.49–1.81 (m, 6H, 6CH2, cy-Oct + 4H, 2CH2, piperidine), 1.95–2.11 (m, 2H, 2CH2, cy-Oct), 2.14–2.34 (m, 2H, CH2N), 2.54 (br.s, 4H, 2CH2N, piperidine), 3.29 (s, 2H, CH2O). 13C NMR (δ, ppm): 18.9 (2CH2, cy-Oct), 24.1 (CH2, piperidine), 26.1 (2CH2, piperidine), 29.9 (2CH2, cy-Oct), 32.0 (2CH2, cy-Oct), 56.8 (2CH2N, piperidine), 70.2 (CH2N), 71.7 (CH2OH), 72.0 (C-CH2OH), 73.6 (C-CH2N). HRMS (ESI+, m/z): calculated for C15H27NO2 [M + H]+: 254.2115, found: 254.2119.
[5-(Pyrrolidin-1-ylmethyl)-9-oxabicyclo[3.3.1]nonan-1-yl]methanol (5e). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:5. Yield 83% (20 mg), yellow oil, Rf 0.24 (light petrol:DCM:MeOH 1:4:1). 1H NMR (δ, ppm): 1.32–1.40 (m, 2H, 2CH2, cy-Oct), 1.44–1.52 (m, 2H, 2CH2, cy-Oct), 1.58–1.76 (m, 6H, 6CH2, cy-Oct), 1.78–1.92 (m, 4H, 2CH2, pyrrolidine), 1.96–2.13 (m, 2H, 2CH2, cy-Oct), 2.56 (br.s, 2H, CH2N), 2.82 (br.s, 4H, 2CH2N, pyrrolidine), 3.32 (br.s, 2H, 2CH2OH, pyrrolidine). 13C NMR (δ, ppm): 18.8 (2CH2, cy-Oct), 23.8 (2CH2, pyrrolidine), 29.6 (2CH2, cy-Oct), 32.1 (2CH2, cy-Oct), 56.5 (2CH2, pyrrolidine), 68.1 (CH2N), 71.5 (CH2OH), 72.3 (C-CH2N), 72.8 (C-CH2OH). HRMS (ESI+, m/z): calculated for C14H25NO2 [M + H]+:240.1958, found: 240.1961.
1,5-Bis[(dibutylamino)methyl]cyclooctane-1,5-diol (5f). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:5. Yield 83% (25 mg), yellow oil, Rf 0.16 (EtOAc). 1H NMR (δ, ppm, J, Hz): 0.89 (t, 3J = 7.2, 6H, 2CH3, Bu), 1.20–1.31 (m, 4H, 2CH2, Bu), 1.31–1.45 (m, 8H, 4CH2, cy-Oct + 2CH2, Bu), 1.56–1.77 (m, 6H, 6CH2, cy-Oct), 1.95–2.08 (m, 2H, 2CH2, cy-Oct), 2.30 (s, 2H, CH2N), 2.44–2.57 (m, 4H, 2CH2N, Bu), 3.28 (s, 2H, CH2O). 13C NMR (δ, ppm): 14.3 (2CH3, Bu), 18.9 (2CH2, cy-Oct), 20.8 (2CH2, Bu), 29.5 (2CH2, Bu), 29.8 (2CH2, cy-Oct), 31.8 (2CH2, cy-Oct), 56.1 (2CH2N, Bu), 66.3 (CH2N), 71.7 (CH2O), 72.1 (C-CH2O), 73.8 (C-CH2N). HRMS (ESI+, m/z): calculated for C18H35NO2 [M + H]+: 298.2741, found: 298.2725.
{5-[(Propargylamino)methyl]-9-oxabicyclo[3.3.1]nonan-1-yl}methanol (5g). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 70% (16 mg), yellow oil, Rf 0.32 (light petrol:EtOAc:MeOH 1:1:1). 1H NMR (δ, ppm, J, Hz): 1.30–1.40 (m, 2H, 2CH2, cy-Oct), 1.41–1.52 (m, 2H, 2CH2, cy-Oct), 1.57–1.74 (m, 6H, 6CH2, cy-Oct), 1.95–2.10 (m, 2H, 2CH2, cy-Oct), 2.28 (t, 4J = 2.4, 1H, CH, propargyl), 2.67 (s, 2H, CH2N), 3.06 (br.s, 2H, NH, OH), 3.35 (s, 2H, CH2O), 3.54 (d, 4J = 2.4 Hz, CH2, propargyl). 13C NMR (δ, ppm): 18.4 (2CH2, cy-Oct), 29.7 (2CH2, cy-Oct), 31.6 (2CH2, cy-Oct), 38.5 (CH2, propargyl), 59.8 (CH2N), 71.3 (CH2OH), 71.7 (C-CH2N), 72.6 (C-CH2O), 72.8 (CH, propargyl), 80.9 (C, propargyl). HRMS (ESI+, m/z): calculated for C13H21NO2 [M + H]+: 224.1645, found: 224.1649.
{5-[(Benzylamino)methyl]-9-oxabicyclo[3.3.1]nonan-1-yl}methanol (5h). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 80% (22 mg), yellow oil, Rf 0.39 (light petrol:EtOAc:MeOH 1:1:0.5). 1H NMR (δ, ppm): 1.27–1.36 (m, 2H, 2CH2, cy-Oct), 1.37–1.50 (m, 2H, 2CH2, cy-Oct), 1.54–1.71 (m, 6H, 4CH2, cy-Oct), 1.89–2.03 (m, 2H, 2CH2, cy-Oct), 2.57 (s, 2H, CH2N), 3.31 (s, 2H, CH2O), 4.00 (s, 2H, PhCH2N), 4.10 (br.s, 2H, NH+OH), 7.28–7.41 (m, 5H, 5CH, Ph). 13C NMR (δ, ppm): 18.5 (2CH2, cy-Oct), 29.7 (2CH2, cy-Oct), 31.7 (2CH2, cy-Oct), 53.7 (PhCH2N), 60.0 (CH2N), 71.5 (CH2OH), 71.8 (C), 72.6 (C), 127.5 (CH, Ph), 128.7 (4CH, Ph), 138.7 (C, Ph). HRMS (ESI+, m/z): calculated for C17H25NO2 [M + H]+: 276.1958, found: 276.1965.
(5-{[(4-Ethylbenzyl)amino]methyl}-9-oxabicyclo[3.3.1]nonan-1-yl)methanol (5i). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 65% (20 mg), yellow oil, Rf 0.78 (light petrol:DCM:MeOH 1:1:0.5). 1H NMR (δ, ppm, J, Hz): 1.23 (t, 3H, 3J 7.6, CH3), 1.25–1.34 (m, 2H, 2CH2, cy-Oct), 1.38–1.49 (m, 2H, 2CH2, cy-Oct), 1.56–1.74 (m, 6H, 6CH2, cy-Oct), 1.91–2.06 (m, 2H, 2CH2, cy-Oct), 2.55 (s, 2H, CH2N), 2.64 (q, 2H, 3J 7.6, CH2, Et), 3.26 (s, 2H, CH2O), 3.77 (br.s, 2H, NH+OH), 3.93 (s, 2H, ArCH2N), 7.15–7.20 (m, 2H, 2CH, Ar), 7.30–7.36 (m, 2H, 2CH, Ar). 13C NMR (δ, ppm): 15.7 (CH3), 18.4 (2CH2, cy-Oct), 28.7 (CH2, Et), 29.6 (2CH2, cy-Oct), 31.7 (2CH2, cy-Oct), 53.3 (ArCH2N), 59.5 (CH2N), 71.2 (CH2OH), 71.3 (C-CH2N), 72.8 (C-CH2OH), 128.3 (2CH, Ar), 129.0 (2CH, Ar), 134.4 (C, Ar), 143.9 (C, Ar). HRMS (ESI+, m/z): calculated for C19H29NO2 [M + H]+: 304.2271, found: 304.2272.
[5-({[4-(Trifluoromethyl)benzyl])amino}methyl)-9-oxabicyclo[3.3.1]nonan-1-yl]methanol (5j). Reaction time—10 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 40% (13 mg), yellow oil, Rf 0.24 (light petrol:EtOAc 1:1). 1H NMR (δ, ppm, J, Hz): 1.31–1.46 (m, 4H, 4CH2, cy-Oct), 1.55–1.78 (m, 6H, 6CH2, cy-Oct), 1.93–2.09 (m, 2H, 2CH2, cy-Oct), 2.47 (s, 2H, CH2N), 3.31 (s, 2H, CH2O), 3.87 (s, 2H, ArCH2N), 7.41–7.50 (m, 2H, 2CH, Ar), 7.54–7.60 (m, 2H, 2CH, Ar). 13C NMR (δ, ppm, J, Hz): 18.6 (2CH2, cy-Oct), 29.9 (2CH2, cy-Oct), 31.8 (2CH2, cy-Oct), 53.7 (ArCH2N), 61.0 (CH2N), 71.6 (CH2OH), 72.3 (C), 72.4 (C), 124.5 (q, 1JCF 272), 125.4 (q, 3JCF 4, 2CH, Ar), 128.3 (2CH, Ar), 129.3 (q, 2JCF 32, C, Ar), 145.0 (C, Ar). 19F NMR (δ, ppm): −62.37 (s, 3F). HRMS (ESI+, m/z): calculated for C18H24F3NO2 [M + H]+: 344.1832, found: 344.1836.
[5-({[4-(3-Methylpiperidin-1-yl)benzyl]amino}methyl)-9-oxabicyclo[3.3.1]non-1-yl]methanol (5k). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 16% (6 mg), yellow oil, Rf 0.78 (light petrol:DCM:MeOH 1:1:0.5). 1H NMR (δ, ppm, J, Hz): 0.94 (d, 3H, 3J 6.6, CH3), 0.99–1.13 (m, 1H, CH2, piperidine), 1.19–1.35 (m, 2H, cy-Oct), 1.40–1.51 (m, 2H, 2CH2, cy-Oct), 1.50–1.87 (m, 10H, 6CH2, cy-Oct + 2CH2 piperidine + CH, piperidine), 1.88–2.09 (m, 2H, 2CH2, cy-Oct), 2.31–2.41 (m, 1H, CH2N, piperidine), 2.60–2.73 (m, 1H, CH2N, piperidine), 2.76 (s, 2H, CH2N), 3.34 (s, 2H, CH2O), 3.54–3.69 (m, 2H, 2CH2N, piperidine), 4.26 (s, 2H, ArCH2N), 6.86–6.96 (m, 2H, 2CH, Ar), 7.36–7.38 (d, 2H, 2CH, Ar), 7.89 (br.s, 2H, NH+OH). 13C NMR (δ, ppm): 18.1 (2CH2, cy-Oct), 19.6 (CH3), 25.2 (CH2, piperidine), 28.9 (2CH2, cy-Oct), 30.9 (CH, piperidine), 31.3 (2CH2, cy-Oct), 33.0 (CH2, piperidine), 49.2 (CH2, piperidine), 51.7 (ArCH2N), 55.7 (CH2N), 56.9 (CH2, piperidine), 69.4 (C-CH2N), 70.7 (CH2OH), 73.8 (C-CH2OH), 116.1 (2CH, Ar), 118.9 (C, Ar), 131.6 (2CH, Ar), 152.5 (C, Ar). HRMS (ESI+, m/z): calculated for C23H36N2O2 [M + H]+: 373.2850, found: 373.2852.
{5-[(Phenylamino)methyl]-9-oxabicyclo[3.3.1]nonan-1-yl}methanol (5l). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 36% (9 mg), yellow oil, Rf 0.77 (light petrol:EtOAc 1:2). 1H NMR (δ, ppm): 1.35–1.43 (m, 2H, 2CH2, cy-Oct), 1.44–1.53 (m, 2H, 2CH2, cy-Oct), 1.59–1.79 (m, 6H, 4CH2, cy-Oct), 1.97–2.11 (m, 2H, 2CH2, cy-Oct), 3.03 (s, 2H, CH2N), 3.35 (s, 2H, CH2O), 6.58–6.73 (m, 3H, 3CH, Ph), 7.12–7.19 (m, 2H, 2CH, Ph). 13C NMR (101 MHz, CDCl3) δ, ppm: 18.5 (2CH2, cy-Oct), 29.8 (2CH2, cy-Oct), 31.6 (2CH2, cy-Oct), 55.4 (CH2N), 71.5 (CH2OH), 72.4 (C), 72.5 (C), 113.0 (2CH, Ph), 117.3 (CH, Ph), 129.3 (2CH, Ph), 148.9 (C, Ph). HRMS (ESI+, m/z): calculated for C16H23NO2 [M + H]+: 262.1802, found: 262.1806.
{5-[(4-Methoxyphenylamino)methyl]-9-oxabicyclo[3.3.1]nonan-1-yl}methanol (5m). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 95% (27 mg), yellow oil, Rf 0.32 (EtOAc:DCM 1:5). 1H NMR (δ, ppm): 1.34–1.42 (m, 2H, 2CH2, cy-Oct), 1.43–1.53 (m, 2H, 2CH2, cy-Oct), 1.59–1.81 (m, 6H, 6CH2, cy-Oct), 1.96–2.10 (m, 2H, 2CH2, cy-Oct), 2.97 (s, 2H, CH2N), 3.35 (s, 2H, CH2O), 3.74 (s, 3H, OMe), 6.56–6.64 (m, 2H, 2CH, Ar), 6.74–6.80 (m, 2H, 2CH, Ar). 13C NMR (δ, ppm): 18.5 (2CH2, cy-Oct), 29.9 (2CH2, cy-Oct), 31.7 (2CH2, cy-Oct), 56.0 (OMe), 56.5 (CH2N), 71.6 (CH2O), 72.4 (C-CH2NH), 72.5 (C-CH2OH), 114.3 (2CH, Ar), 115.1 (2CH, Ar), 143.3 (C-NH, Ar), 152.1 (C-O, Ar). HRMS (ESI+, m/z): calculated for C17H25NO3 [M + H]+: 292.1907, found: 292.1911.
{5-[(4-Methylphenylamino)methyl]-9-oxabicyclo[3.3.1]nonan-1-yl}methanol (5n). Reaction time—10 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 26% (7 mg), yellow oil, Rf 0.67 (light petrol:EtOAc 1:1). 1H NMR (δ, ppm): 1.32–1.42 (m, 2H, 2CH2, cy-Oct), 1.43–1.53 (m, 2H, 2CH2, cy-Oct), 1.57–1.82 (m, 6H, 4CH2, cy-Oct), 1.95–2.11 (m, 2H, 2CH2, cy-Oct), 2.23 (s, 3H, CH3), 3.00 (s, 2H, CH2N), 3.35 (s, 2H, CH2O), 6.52–6.58 (m, 2H, 2CH, Ar), 6.93–7.01 (m, 2H, 2CH, Ar). 13C NMR (δ, ppm): 18.5 (2CH2, cy-Oct), 20.5 (CH3), 29.8 (2CH2, cy-Oct), 31.6 (2CH2, cy-Oct), 55.7 (CH2N), 71.6 (CH2OH), 72.4 (C), 72.5 (C), 113.1 (2CH, Ar), 126.4 (C, Ar), 129.8 (2CH, Ar), 146.7 (C, Ar). HRMS (ESI+, m/z): calculated for C17H25NO2 [M + H]+: 276.1958, found: 276.1966.
{5-[(4-Bromophenylamino)methyl]-9-oxabicyclo[3.3.1]nonan-1-yl}methanol (5o). Reaction time—30 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 17% (6 mg), yellow oil, Rf 0.58 (light petrol:EtOAc 1:1). 1H NMR (δ, ppm): 1.34–1.43 (m, 2H, 2CH2, cy-Oct), 1.43–1.52 (m, 2H, 2CH2, cy-Oct), 1.58–1.75 (m, 6H, 4CH2, cy-Oct), 1.97–2.12 (m, 2H, 2CH2, cy-Oct), 2.98 (s, 2H, CH2N), 3.35 (s, 2H, CH2O), 6.45–6.54 (m, 2H, 2CH, Ar), 7.19–7.26 (m, 2H, 2CH, Ar). 13C NMR (δ, ppm): 18.5 (2CH2, cy-Oct), 29.8 (2CH2, cy-Oct), 31.6 (2CH2, cy-Oct), 55.3 (CH2N), 71.6 (CH2OH), 72.4 (C), 72.6 (C), 108.7 (C, Ar), 114.5 (2CH, Ar), 132.0 (2CH, Ar), 148.0 (C, Ar). HRMS (ESI+, m/z): calculated for C16H22BrNO2 [M + H]+: 340.0907, found: 340.0916.
1,5-Bis[(butylamino)methyl]cyclooctane-1,5-diol (6a). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 56% (19 mg), yellow oil, Rf 0.05 (CH3CN). 1H NMR (δ, ppm, J, Hz): 0.90 (t, 6H, 3J 7.2, 2CH3), 1.29–1.38 (m, 4H, 2CH2, Bu), 1.39–1.50 (m, 10H, 6CH2, cy-Oct + 2CH2, Bu), 1.77–1.90 (m, 6H, 6CH2, cy-Oct), 2.46 (s, 4H, 2CH2N), 2.62 (t, 4H, 3J 7.1, 2CH2N, Bu). 13C NMR (δ, ppm): 14.1 (2CH3, Bu), 18.8 (2CH2, cy-Oct), 20.5 (2CH2, Bu), 32.6 (2CH2, Bu), 37.5 (4CH2, cy-Oct), 50.5 (2CH2N, Bu), 60.5 (2CH2N), 72.8 (2C). HRMS (ESI+, m/z): calculated for C18H38N2O2 [M + H]+: 315.3006, found: 315.3015.
1,5-Bis(morpholin-4-ylmethyl)cyclooctane-1,5-diol (6b). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:5. Yield 97% (33 mg), yellow oil, Rf = 0.61 (light petrol:EtOAc:MeOH 3:1:1). 1H NMR (δ, ppm): 1.37–1.54 (m, 6H, 6CH2, cy-Oct), 1.79–1.95 (m, 6H, 6CH2, cy-Oct), 2.26 (s, 4H, 2CH2N), 2.60–2.63 (m, 8H, 4CH2N, morpholine), 2.99 (br.s, 2H, 2OH), 3.68–3.71 (m, 8H, 4CH2O, morpholine). 13C NMR (δ, ppm): 18.4 (2CH2, cy-Oct), 37.9 (4CH2, cy-Oct), 56.3 (4CH2N, morpholine), 67.5 (4CH2O, morpholine), 69.0 (2CH2N), 74.0 (2C). HRMS (ESI+, m/z): calculated for C18H34N2O4 [M + H]+: 343.2591, found: 343.2596.
1,5-Bis(azepan-4-ylmethyl)cyclooctane-1,5-diol (6c). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:5. Yield 19% (7 mg), yellow oil, Rf 0.08 (light petrol:DCM:MeOH 1:3:1). 1H NMR (δ, ppm): 1.38–1.52 (m, 6H, 6CH2, cy-Oct), 1.53–1.71 (m, 16H, 8CH2, azepane), 1.78–1.96 (m, 6H, 6CH2, cy-Oct), 2.43 (s, 4H, 2CH2N), 2.74–2.86 (m, 8H, 4CH2N, azepane). 13C NMR (δ, ppm): 18.7 (2CH2, cy-Oct), 27.1 (4CH2, azepane), 29.1 (4CH2, azepane), 37.8 (4CH2, cy-Oct), 59.2 (4CH2N, azepane), 68.8 (2CH2N), 73.7 (2C). HRMS (ESI+, m/z): calculated for C22H42N2O2 [M + H]+: 367.3319, found: 367.3319.
1,5-Bis(piperidin-4-ylmethyl)cyclooctane-1,5-diol (6d). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:5. Yield 97% (30 mg), yellow oil, Rf 0.09 (light petrol:DCM:MeOH 1:3:2). 1H NMR (δ, ppm): 1.35–1.53 (m, 6H, 6CH2, cy-Oct + 4H, 2CH2, piperidine), 1.53–1.65 (m, 8H, 4CH2, piperidine), 1.79–1.95 (m, 6H, 6CH2, cy-Oct), 2.29 (s, 4H, 2CH2N), 2.61 (br.s, 8H, 4CH2N, piperidine). 13C NMR (δ, ppm): 18.5 (2CH2, cy-Oct), 23.9 (2CH2, piperidine), 26.3 (4CH2, piperidine), 38.0 (4CH2, cy-Oct), 57.4 (4CH2N, piperidine), 68.6 (2CH2N), 73.3 (2C). HRMS (ESI+, m/z): calculated for C20H38N2O2 [M + H]+: 339.3006, found 339.3003.
1,5-Bis(pyrrolidin-4-ylmethyl)cyclooctane-1,5-diol (6e). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:5. Yield 61% (23 mg), yellow oil, Rf 0.1 (light petrol:DCM:MeOH 1:1:1). 1H NMR (δ, ppm): 1.40–1.57 (m, 6H, 6CH2, cy-Oct), 1.68–1.79 (m, 8H, 4CH2, pyrrolidine), 1.80–1.94 (m, 6H, 6CH2, cy-Oct), 2.45 (s, 4H, 2CH2N), 2.62–2.74 (m, 8H, 4CH2N, pyrrolidine). 13C NMR (δ, ppm): 18.6 (2CH2, cy-Oct), 24.3 (4CH2, pyrrolidine), 38.0 (4CH2, cy-Oct), 57.0 (4CH2, pyrrolidine), 67.2 (2CH2N), 73.4 (2C). HRMS (ESI+, m/z): calculated for C18H34N2O2 [M + H]+: 311.2693, found: 311.2701.
1,5-Bis[(dibutylamino)methyl]cyclooctane-1,5-diol (6f). Reaction time—20 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:5. Yield 65% (28 mg), yellow oil, Rf 0.24 (light petrol:DCM:MeOH 1:4:1). 1H NMR (CD3OD; δ, ppm, J, Hz): 0.96 (t, 3J = 7.3, 12H, 4CH3, Bu), 1.25–1.42 (m, 8H, 4CH2, Bu), 1.46–1.64 (m, 14H, 6CH2, cy-Oct + 4CH2, Bu), 1.85–1.98 (m, 6H, 6CH2, cy-Oct), 2.64 (br.s, 4H, 2CH2N), 2.79 (br.s, 8H, 4CH2N, Bu). 13C NMR (CD3OD; δ, ppm): 14.3 (4CH3, Bu), 18.8 (2CH2, cy-Oct), 21.4 (4CH2, Bu), 29.0 (4CH2, Bu), 38.4 (4CH2, cy-Oct), 57.2 (4CH2N, Bu), 66.5 (2CH2N), 74.6 (2C). HRMS (ESI+, m/z): calculated for C26H54N2O2 [M + H]+: 427.4258, found: 427.4282.
1,5-Bis[(phenylamino)methyl]cyclooctane-1,5-diol (6l). Reaction time—5 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 6% (2 mg), yellow oil, Rf 0.58 (light petrol:EtOAc 2:1). 1H NMR (δ, ppm): 1.56–1.71 (m, 6H, 6CH2, cy-Oct), 1.83–1.93 (m, 2H, 2CH2, cy-Oct), 1.93–2.04 (m, 4H, 4CH2, cy-Oct), 3.05 (s, 4H, 2CH2N), 6.59–6.77 (m, 6H, 6CH, Ph), 7.12–7.20 (m, 4H, 4CH, Ph). 13C NMR (δ, ppm): 18.5 (2CH2, cy-Oct), 37.3 (4CH2, cy-Oct), 55.9 (2CH2, CH2N), 74.2 (2C), 113.4 (4CH, Ar), 118.0 (2CH, Ar), 129.4 (4CH, Ar), 148.9 (2C, Ar). HRMS (ESI+, m/z): calculated for C22H30N2O2 [M + H]+: 355.2380, found: 355.2388.
1,5-Bis[(4-bromophenylamino)methyl]cyclooctane-1,5-diol (6o). Reaction time—40 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 4% (2 mg), yellow oil, Rf 0.32 (light petrol:EtOAc 1:2). 1H NMR (δ, ppm): 1.50–1.69 (m, 6H, 6CH2, cy-Oct), 1.79–1.91 (m, 2H, 2CH2, cy-Oct), 1.91–2.02 (m, 4H, 4CH2, cy-Oct), 3.00 (s, 4H, 2CH2N), 6.49–6.59 (m, 4H, 4CH, Ar), 7.20–7.29 (m, 4H, 4CH, Ph). 13C NMR (δ, ppm): 18.4 (2CH2, cy-Oct), 37.3 (4CH2, cy-Oct), 55.8 (2CH2, CH2N), 74.2 (2C), 109.4 (2C, Ar), 114.9 (4CH, Ar), 132.1 (4CH, Ar), 147.9 (C, Ar). HRMS (ESI+, m/z): calculated for C22H28Br2N2O2 [M + H]+: 511.0590, found: 511.0587.
Molecules 31 00252 i016
7-({[(4-Trifluoromethyl)benzyl]amino}methyl)-1-oxaspiro[2.7]decan-7-ol (7j). Reaction time—10 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 7% (2 mg), yellow oil, Rf 0.16 (EtOAc). 1H NMR (δ, ppm): 1.38–1.49 (m, 4H, 2CH2, cy-Oct), 1.56–1.87 (m, 8H, 6CH2, cy-Oct), 2.55 (s, 2H, CH2O), 2.60 (s, 2H, CH2N), 3.90 (s, 2H, ArCH2N), 7.37–7.48 (m, 2H, 2CH, Ar), 7.54–7.64 (m, 2H, 2CH, Ar). 13C NMR (δ, ppm): 19.3 (2CH2, cy-Oct), 34.9 (2CH2, cy-Oct), 35.9 (2CH2, cy-Oct), 54.1 (CH2N), 55.3 (CH2O), 58.1 (ArCH2N), 59.1 (C, epoxy), 73.8 (C-OH), 125.5 (q, 3JCF 4, 2CH, Ar), 128.4 (2CH, Ar). Signals of CF3-group and quaternary carbon atoms were not observed due to low concentration of the compound. 19F NMR (δ, ppm): −62.44 (c, 3F). HRMS (ESI+, m/z): calculated for C18H24F3NO2 [M + H]+: 344.1832, found: 344.1827.
Molecules 31 00252 i017
7-{[(4-Bromophenyl)amino]methyl}-1-oxaspiro[2.7]decan-7-ol (7o). Reaction time—40 h. Reagent ratio (bis(oxirane):amine:LiClO4)—1:2.2:20. Yield 6% (2 mg), yellow oil, Rf 0.39 (light petrol:EtOAc 1:1). 1H NMR (δ, ppm): 1.47–1.92 (m, 12H, 6CH2, cy-Oct), 2.63 (s, 2H, CH2O), 3.04 (s, 2H, CH2N), 7.48–7.58 (m, 2H, 2CH, Ar), 7.19–7.26 (m, 2H, 2CH, Ar). 13C NMR (δ, ppm): 19.4 (2CH2, cy-Oct), 34.9 (2CH2, cy-Oct), 35.8 (2CH2, cy-Oct), 53.5 (CH2N), 55.5 (CH2O), 59.0 (C, epoxy), 75.1 (C-OH), 109.2 (C, Ar), 114.8 (2CH, Ar), 132.1 (2CH, Ar), 147.9 (C, Ar). HRMS (ESI+, m/z): calculated for C16H22BrNO2 [M + H]+: 340.0907, found: 340.0915.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/molecules31020252/s1; Table S1: Optimization of ring-opening conditions; copies of NMR spectra of the obtained compounds.

Author Contributions

Conceptualization, E.B.A. and K.N.S.; methodology, E.B.A. and K.N.S.; validation, K.N.S. and Y.K.G.; investigation, O.V.R., D.V.S., S.V.K., Y.K.G. and O.A.M.; data curation, K.N.S.; writing—original draft preparation, K.N.S.; writing—review and editing, E.B.A.; visualization, K.N.S. and Y.K.G.; supervision, E.B.A.; project administration, E.B.A. All authors have read and agreed to the published version of the manuscript.

Funding

This study was performed within the framework of the state assignment (No. 121021000105-7, Molecular design, synthesis, and study of physiologically active compounds, advancing the methodology of medicinal chemistry, chemoinformatics, and targeted chemical synthesis).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data is contained within the article or Supplementary Materials.

Acknowledgments

The research was carried out using the NMR spectrometer Agilent 400-MR and mass-spectrometer G3 QTof quadrupole-time-of-flight purchased under the program of M.V. Lomonosov Moscow State University development.

Conflicts of Interest

The authors declare no conflicts of interest.

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Molecules 31 00252 g001
Figure 1. Examples of bioactive compounds containing aminoalcohol scaffolds.
Figure 1. Examples of bioactive compounds containing aminoalcohol scaffolds.
Molecules 31 00252 g001
Molecules 31 00252 sch001
Scheme 1. Ring-opening of bis(oxiranes) trans-1 and cis-1 with sodium azide [18].
Scheme 1. Ring-opening of bis(oxiranes) trans-1 and cis-1 with sodium azide [18].
Molecules 31 00252 sch001
Molecules 31 00252 g002
Figure 2. Examples of medicinal drugs and bioactive natural compounds containing bicyclo[3.3.1]nonane and related scaffolds.
Figure 2. Examples of medicinal drugs and bioactive natural compounds containing bicyclo[3.3.1]nonane and related scaffolds.
Molecules 31 00252 g002
Molecules 31 00252 sch002
Scheme 2. Ring-opening of bis(oxiranes) trans-1 and cis-1 with n-butylamine, morpholine, and azepane; amines used as solvent.
Scheme 2. Ring-opening of bis(oxiranes) trans-1 and cis-1 with n-butylamine, morpholine, and azepane; amines used as solvent.
Molecules 31 00252 sch002
Table 1. Ring-opening of bis(oxiranes) trans-1 and cis-1 with various amines.
Table 1. Ring-opening of bis(oxiranes) trans-1 and cis-1 with various amines.
Molecules 31 00252 i001
Starting
Material		NHR1R2ProductYield, % 1ProductYield, % 1
trans-1 + cis-1NH2Bu5a816a–
cis-1NH2Bu––6a65
trans-1 + cis-1Molecules 31 00252 i0025b886b97
trans-1 + cis-1Molecules 31 00252 i0035c546c19
trans-1 + cis-1Molecules 31 00252 i0045d836d–
cis-1Molecules 31 00252 i005––6d97
trans-1 + cis-1Molecules 31 00252 i0065e836e–
cis-1Molecules 31 00252 i007––6e61
trans-1NHBu25f83––
cis-1NHBu2––6f65
trans-1 + cis-1HC≡CCH2NH25g706g–
trans-1 + cis-1PhCH2NH25h806h–
trans-1 + cis-1Molecules 31 00252 i0085i656i–
trans-1Molecules 31 00252 i0095j40––
cis-1Molecules 31 00252 i010––6j– 2
trans-1 + cis-1Molecules 31 00252 i0115k166k–
trans-1 + cis-1PhNH25l366l6
trans-1 + cis-1Molecules 31 00252 i0125m956m–
trans-1 + cis-1Molecules 31 00252 i0135n266n–
trans-1 + cis-1Molecules 31 00252 i0145o176o–
cis-1Molecules 31 00252 i015––6o2 2
1 Isolated yields, taking in account the ratio of starting diastereomers trans-1 and cis-1. 2 The products of opening of one oxirane ring 7j,o (see Section 3.2) were obtained.
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Ryzhikova, O.V.; Savchenkova, D.V.; Kositov, S.V.; Grishin, Y.K.; Maloshitskaya, O.A.; Sedenkova, K.N.; Averina, E.B. Straightforward Synthetic Approach to Aminoalcohols with 9-oxabicyclo[3.3.1]nonane or Cyclooctane Core via Nucleophilic Ring-Opening of Spirocyclic Bis(oxiranes). Molecules 2026, 31, 252. https://doi.org/10.3390/molecules31020252

AMA Style

Ryzhikova OV, Savchenkova DV, Kositov SV, Grishin YK, Maloshitskaya OA, Sedenkova KN, Averina EB. Straightforward Synthetic Approach to Aminoalcohols with 9-oxabicyclo[3.3.1]nonane or Cyclooctane Core via Nucleophilic Ring-Opening of Spirocyclic Bis(oxiranes). Molecules. 2026; 31(2):252. https://doi.org/10.3390/molecules31020252

Chicago/Turabian Style

Ryzhikova, Olga V., Daiana V. Savchenkova, Sergey V. Kositov, Yuri K. Grishin, Olga A. Maloshitskaya, Kseniya N. Sedenkova, and Elena B. Averina. 2026. "Straightforward Synthetic Approach to Aminoalcohols with 9-oxabicyclo[3.3.1]nonane or Cyclooctane Core via Nucleophilic Ring-Opening of Spirocyclic Bis(oxiranes)" Molecules 31, no. 2: 252. https://doi.org/10.3390/molecules31020252

APA Style

Ryzhikova, O. V., Savchenkova, D. V., Kositov, S. V., Grishin, Y. K., Maloshitskaya, O. A., Sedenkova, K. N., & Averina, E. B. (2026). Straightforward Synthetic Approach to Aminoalcohols with 9-oxabicyclo[3.3.1]nonane or Cyclooctane Core via Nucleophilic Ring-Opening of Spirocyclic Bis(oxiranes). Molecules, 31(2), 252. https://doi.org/10.3390/molecules31020252

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