Stereoselective total synthesis of the antitumor antibiotic (-)-bactobolin

Synthetic Approaches to N‐Methoxy‐N‐methylamides

“…Compound 22 was acylated further with CH 3 MgBr, followed by deprotection of the TBS group with n-Bu 4 NF, to give the corresponding methyl ketone (23) (Scheme 14). 28 The functionality of the five-membered lactones was also opened with an aluminum amide reagent. 29 For example, the treatment of five-membered lactone (24) with in situ (N-methoxy-N-methyl) dimethyl aluminum gave the corresponding N-Boc protected (S)-N-methoxy-N-methyl 4-hydroxybutanamide (25) (Scheme 15(a)).…”

“…Compound 22 was acylated further with CH 3 MgBr, followed by deprotection of the TBS group with n ‐Bu 4 NF, to give the corresponding methyl ketone ( 23 ) (Scheme 14). 28 …”

2‐(Trimethylsilyl)ethanesulfonyl (or SES) Group in Amine Protection and Activation

“…The process was optimized by the group of Kim 60 for tosylamine and various amines (Scheme 8) and used to form the SES-NSO 7 by Weinreb and co-workers. 61,62 After formation of SES-NSO 7, the sulfonylimine 6 is quickly and easily obtained, 58,59,[61][62][63] sulfur dioxide being the only reaction byproduct (eq 8).…”

“…Weinreb and co-workers developed in 1988 the reductive sulfonamidation 58,63 for the synthesis of two antibiotics, Actinobolin and Bactobolin. Due to steric hindrance, the amine, resulting from the reductive amination of the corresponding R-keto lactone, was unable to undergo the expected sulfonylation (Scheme 10).…”

“…Surprisingly, the N-(Z)-SES sulfonamide 41 is obtained under more drastic conditions (benzyl chloroformate in the presence of MeLi followed by NaH). Cyclic carbamates were also synthesized from -aminohydroxides under roughly the same conditions as those for N-(Boc)-SES sulfonamide (Scheme 40) and used in the total syntheses of Bactoboline 58,63,120 and Luzopeptine. 121…”