Synthetic approaches towards the novel 1,3-dioxo-1,2-dithiolane moiety in the antitumour antibiotic substance leinamycin

Abstract

A number of complementary synthetic approaches t o the P-thiolactone intermediate 9 for elaboration to the novel 1,3-dioxo-1,2-dithiolane moiety 6 found in the antitumour antibiotic substance leinamycin 1 are described.Thus, deprotection of the benzylthio ether produced from 3-methylbut-2-enoic acid and toluenea-thiol, leads to the mercapto acid 12 which on cyclisation produces the thiolactone 13. a-Methylation of the thiolactone 13, followed by a-oxygenation then gives rise t o the substituted f3-thiolactone 9. The P-thiolactone 9 is also produced when: (i) the sodium glycidate 17 is stirred with sodium sulfide leading to 18, followed by thiolactonisation; (ii) thioacetone is treated with the ketene derived from 2-acetoxypropanoyl chloride; and (iii) by irradiation of 3-methyl-2-trimethylsilyloxybut-2-ene 22 with thiophosgene leading to 23, followed by hydrolysis.

Synthesis and characterization of a small analogue of the anticancer natural product leinamycin

“…Our approach represents a modified version of the route pioneered by Pattenden and Shuker for the synthesis of simple 1,2-dithionlan-3-one 1-oxides. 31 A similar route was used by Lee et al . for the preparation of analogues containing a pendent alkene.…”

“…Our synthesis expands the scope of a route developed by Pattenden and Shuker for simple 1,2-dithiolan-3-one 1-oxides such as 11 and 12 related to leinamycin. 31 A similar approach was used by Lee et al . to prepare a leinamycin analogue similar to 19 bearing a pendent alkene; however, these researchers did not report the reactions of their product with thiols or DNA.…”

Four‐Membered Heterocycles: Structure and Reactivity

“…Thietan-2-ones are formed by the reaction of 3-mercaptocarboxylic acids with DCC [249], i butyl chloroformate [250], methyl chloroformate [251], Ac 2 O [252], diethyl cyanophosphonate [253] or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDAC) (Scheme 3.139) [254].…”

“…The potassium enolate of a thietan-2-one reacts with MoO 5 to give the corresponding a-hydroxythietanone (Scheme 3.186) [253]. …”

“…These acids can be transformed into 1,2-dithiolan-3-ones by reaction with FeCl 3 [253,356] or HIO 3 (Scheme 3.202) [357].…”