Preparation of disulfide and thiosulfinate compounds, useful in peptide synthesis, comprises reacting a silicon-sulfur compound e.g. 2',3'-didesoxy-3'-(2-(trimethylsilyl)ethyl)thiouridine with a thiosulfinate compound

摘要

#CMT# #/CMT# Preparation of disulfide or thiosulfinate compound (I) comprises reacting a silicon-sulfur compound (II) with a thiosulfinate compound (III). #CMT# : #/CMT# Preparation of disulfide or thiosulfinate compound (I) of formula R1-S(O) x-S(O) yR2 comprises reacting a silicon-sulfur compound (II) of formula R1-S(O) x-R3-Si(R4)(R5)(R6) with a thiosulfinate compound (III) of formula R2-S(O) y-X. R1 : hydrocarbon (substituted and/or interrupted by N, O, P, S, Si or halo) e.g. ribonucleoside, 2'-desoxyribonucleoside, 2',3'-didesoxyribonucleosides or 3'-didesoxy-2',3'-deshydroribonucleoside; R2 : R1 or carbon-containing group e.g. 2'-desoxyribonucleoside, 3'-desoxyribonucleoside, 2',3'-didesoxyribonucleoside or 2',3'-didesoxy-2',3'-deshydroribonucleoside; x, y : 0-1; R3 : 2C hydrocarbon (optionally unsaturated and/or substituted), preferably -CH 2-CH 2; R4-R6 : hydrocarbon group, preferably CH 3; and X : halo. Provided that the sum of x and y is not more than 1. #CMT#USE : #/CMT# (I) is useful in peptide synthesis. #CMT#ADVANTAGE : #/CMT# The process avoids side reactions e.g. formation of toxic sulfoxide compound. #CMT#ORGANIC CHEMISTRY : #/CMT# Preferred Process: The process is carried out in the presence of catalytic quantity of fluoride ions obtained ammonium-, tetrabutylammonium- and/or triethylammonium-fluoride. The sulfur atom is connected to 2' or 3' carbon of ribose. #CMT#SPECIFIC COMPOUNDS : #/CMT# The use of 11 compounds is specifically claimed as (II) e.g. 2',3'-didesoxy-3'-(2-(trimethylsilyl)ethyl)thiouridine, 5-bromo-2',3'-didesoxy-3'-(2-(trimethylsilyl)ethyl)thiouridine, desoxy-2'-(2-(trimethylsilyl)ethyl)thiothymidine, 2'-desoxy-3'-(O-mesyl)-2'-(2-(trimethylsilyl)ethyl)thiouridine or 3'-desoxy-3'-(2-(trimethylsilyl)ethyl)thiothymidine. The use of 32 compounds is specifically claimed as (I) e.g. 2',3'-dideshydro-2',3'-didesoxy-2'-(2-(trimethylsilyl)ethyl)thiothymidine, 2',3'-dideshydro-2',3'-didesoxy-3'-(2-trimethylsilyl)ethylthiothymidine, 2',3'-dideshydro-2',3'-didesoxy-2'-(2-trimethylsilyl)ethylthiouridine, 3'-desoxythymidin-3'-yl trichloromethyl disulfide or 2',3'-dideshydro-2',3'-didesoxythymidin-2'-yl trichloromethyl disulfide of formula (Ia). #CMT#EXAMPLE : #/CMT# A solution of 2',3'-dideshydro-2',3'-didesoxy-2'-(2-trimethylsilyl)ethylthiothymidine (50 mg) in anhydrous dichloromethane (3 ml) was refluxed with trichloromethanesulfenyl chloride for 48 hours to give 2',3'-dideshydro-2',3'-didesoxythymidin-2'-yl trichloromethyl disulfide.