(1R,4S,5S)-5-((3-Hydroxypropyl)amino)-4-((1-methyl-1H-tetrazol-5-yl)thio)cyclopent-2-en-1-ol

Using environmentally friendly conditions, the nucleophilic ring-opening reaction of 6-azabicyclo[3.1.0]hex-3-en-2-ol with 1-methyl-1H-tetrazole-5-thiol provided a novel thiol-incorporated aminocyclopentitol, (1R,4S,5S)-5-((3-hydroxypropyl)amino)-4-((1-methyl-1H-tetrazol-5-yl)thio)cyclopent-2-en-1-ol, in excellent yield (95%). The newly synthesized compound was analyzed and characterized via 1H, 13C-NMR, HSQC, and mass spectral data.


Introduction
Aziridines are recurrent motifs in anticancer compounds ( Figure 1A) and are useful building blocks in organic synthesis, largely due to their ring strain [1].
Mannostatin A is a natural product, first isolated from a soil microorganism Streptoverticillus, and is among the most potent inhibitors of class II α-mannosidase. The chemical structure of Mannostatin A contains a thiol functionality, responsible for the high affinity to the enzyme's binding site [12]. Inhibitors of glycosidases are leading the drug discovery across cancer, and viral and bacterial infections. Mannostatin A and its analogs [13] have been used to study the inhibition of glycosidases to orientate the development of drug candidates [6,7].
Mannostatin A is a natural product, first isolated from a soil microorganism Streptoverticillus, and is among the most potent inhibitors of class II α-mannosidase. The chemical structure of Mannostatin A contains a thiol functionality, responsible for the high affinity to the enzyme's binding site [12]. Inhibitors of glycosidases are leading the drug discovery across cancer, and viral and bacterial infections. Mannostatin A and its analogs [13] have been used to study the inhibition of glycosidases to orientate the development of drug candidates [6,7].
Mannostatin A is a natural product, first isolated from a soil microorganism Streptoverticillus, and is among the most potent inhibitors of class II α-mannosidase. The chemical structure of Mannostatin A contains a thiol functionality, responsible for the high affinity to the enzyme's binding site [12]. Inhibitors of glycosidases are leading the drug discovery across cancer, and viral and bacterial infections. Mannostatin A and its analogs [13] have been used to study the inhibition of glycosidases to orientate the development of drug candidates [6,7].
The product 3c was characterized by 1 H-NMR, 13 C-NMR, HSQC, and HRMS. By analyzing the 1 H-NMR spectrum ( Figure S1), we can observe characteristic peaks from product 3c: a singlet at 3.96 ppm, corresponding to the methyl group linked to the tetrazole ring (H-18), and multiplets corresponding to the geminal protons of the thioether at 4.30-4.29 ppm (H-4), the alcohol at 4.59-4.58 ppm (H-1), and the amine at 3.29-3.26 ppm (H-5). The signals for the hydroxypropyl chain can be observed as a quartet (J = 6.9 Hz, 2.77 ppm), a multiplet (1.76-1.67 ppm), and a triplet (J = 6.4 Hz, 3.60 ppm), corresponding to the protons vicinal to the amine (H-7), to the middle-chain methylene (H-8), and to the protons geminal to the hydroxyl group (H-9), respectively. Additionally, the 13 C-NMR ( Figure S2) shows the characteristic peaks from the tetrazole ring: a quaternary carbon at 153.32 ppm (C-13), which does not correlate with a proton signal in the HSQC (Figure S3), and the carbon from the methyl group at 33.87 ppm (C-18).
The product 3c can be further functionalized, since it has a primary and a secondary hydroxyl group. Moreover, 3c has a tetrazole ring which could lead to potential biological activity, since the tetrazole moiety can be found in different approved [21] and candidate drugs [22,23]. Accomplishing the synthesis of 3c contributed to expanding our previous aminocyclopentitols library [17]. Scheme 3. Synthetic pathway from photocyclization of 1-(3-hydroxypropyl)pyridin-1-ium chloride (1c) [18], followed by a nucleophilic attack to the bicyclic vinyl aziridine ring (2c) by 1-methyl-1H-tetrazole-5-thiol to produce 3c.
The product 3c was characterized by 1 H-NMR, 13  The product 3c can be further functionalized, since it has a primary and a secondary hydroxyl group. Moreover, 3c has a tetrazole ring which could lead to potential biological activity, since the tetrazole moiety can be found in different approved [21] and candidate drugs [22,23]. Accomplishing the synthesis of 3c contributed to expanding our previous aminocyclopentitols library [17].

Materials and Methods
All chemicals, reagents, and solvents were of analytical grade, purchased from commercial sources, namely, Merck (Algés, Portugal) and Alfa Aesar (Kandel, Germany) and were used without further purification. NMR spectra were obtained on a Bruker Fourier 300 spectrometer (Bruker BioSpin AG, Fallanden, Switzerland) using TopSpin(®) software (Bruker BioSpin GmbH, Rheinstetten, Germany). NMR experiments were performed in D 2 O at room temperature. Chemical shifts are given in parts per million (ppm); the terms m, s, d, t, and q represent multiplet, singlet, doublet, triplet, and quartet, respectively; and the coupling constants (J) are given in Hertz (Hz). High-resolution mass spectroscopy (HRMS) was performed in a LTQ Orbitrap XL mass spectrometer, Thermo Fischer Scientific, Bremen, Germany.
Supplementary Materials: The following are available online, Figure S1: 1 H NMR spectrum; Figure  S2: 13

Conflicts of Interest:
The authors declare no conflict of interest.