Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives
Abstract
:1. Introduction
2. Materials and Methods
2.1. Microorganisms and Media
2.2. Statistical Analysis
2.3. General Methods of Synthesis α-Hydroxy Phosphonate Derivatives
General Procedure for the Synthesis of α-Hydroxy Phosphonate Derivatives 5–9 and Phosphonate 10
3. Results
3.1. Chemistry
3.2. Cytotoxic Studies of the Library of α-Hydroxy Phosphonate Derivatives
3.3. Analysis of Bacterial DNA Isolated from E. coli R2–R4 Strains Modified with α-Hydroxy Phosphonate Derivatives
3.4. Modification of Plasmid DNA Isolated from E. coli R2–R4 Strains with Tested α-Hydroxy Phosphonate Derivatives
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
MIC | minimum inhibitory concentration |
MBC | minimum bactericidal concentration |
Oc | open circle |
Ccc | covalently closed circle |
BER | base excision repair |
Fpg | DNA-formamidopyrimidine glycosylase |
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Entry | Catalyst | T (°C) | Solvent | Yield [%] e |
---|---|---|---|---|
1 | None | 40 | n-hexane | <1 |
2 | Candida cylindracea lipase (CcL) | 40 | n-hexane | 61 |
3 | Candida cylindracea lipase (CcL) | 40 | TBME | 42 |
4 | Candida cylindracea lipase (CcL) | 40 | DMSO | 12 |
5 | Candida cylindracea lipase (CcL) | 40 | THF | 37 |
6 | Candida cylindracea lipase (CcL) | 40 | toluene | 22 |
7 | Candida cylindracea lipase (CcL) b | 40 | n-hexane | 59 |
8 | Candida cylindracea lipase (CcL) | 30 | n-hexane | 49 |
9 | Candida cylindracea lipase (CcL) | 50 | n-hexane | 54 |
10 | Pseudomonas fluorescens lipase (PfL) | 40 | n-hexane | 13 |
11 | Porcine pancreas lipase (PPL) | 40 | n-hexane | 25 |
12 | Candida rugosa lipase (CrL) | 40 | n-hexane | 39 |
13 | Novozym 435 | 40 | n-hexane | 9 |
14 | Bovine serum albumin (BSA) | 40 | n-hexane | 6 |
15 | Pig liver acetone powder (PLAP) c | 40 | n-hexane | <5 |
16 | Denatured PPL d | 40 | n-hexane | <5 |
No. of Samples | 1 | 2 | 3 | 4 | 5 | 6, 7 | 8, 9 | 10 | Type of Test |
---|---|---|---|---|---|---|---|---|---|
K12 | *** | *** | *** | *** | * | * | * | *** | MIC |
R2 | *** | *** | *** | *** | * | * | * | *** | MIC |
R3 | *** | *** | *** | *** | * | * | * | *** | MIC |
R4 | *** | *** | *** | *** | * | * | * | *** | MIC |
K12 | * | * | ** | * | ** | * | * | ** | MBC |
R2 | ** | * | ** | * | ** | * | * | ** | MBC |
R3 | ** | * | ** | * | ** | * | * | ** | MBC |
R4 | ** | * | ** | * | ** | * | * | ** | MBC |
K12 | *** | * | * | * | * | * | * | *** | MBC/MIC |
R2 | *** | * | * | * | * | * | ** | *** | MBC/MIC |
R3 | *** | * | * | * | * | * | ** | *** | MBC/MIC |
R4 | *** | * | * | * | * | * | ** | *** | MBC/MIC |
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Kowalczyk, P.; Koszelewski, D.; Gawdzik, B.; Samsonowicz-Górski, J.; Kramkowski, K.; Wypych, A.; Lizut, R.; Ostaszewski, R. Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives. Materials 2022, 15, 1975. https://doi.org/10.3390/ma15051975
Kowalczyk P, Koszelewski D, Gawdzik B, Samsonowicz-Górski J, Kramkowski K, Wypych A, Lizut R, Ostaszewski R. Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives. Materials. 2022; 15(5):1975. https://doi.org/10.3390/ma15051975
Chicago/Turabian StyleKowalczyk, Paweł, Dominik Koszelewski, Barbara Gawdzik, Jan Samsonowicz-Górski, Karol Kramkowski, Aleksandra Wypych, Rafał Lizut, and Ryszard Ostaszewski. 2022. "Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives" Materials 15, no. 5: 1975. https://doi.org/10.3390/ma15051975