A Concise Synthesis of the Octalactins

Abstract

The total synthesis of octalactins A and B has been achieved in 15 steps (longest linear sequence) and 10% overall yield from commercially available materials. Key steps include the Paterson-Aldol reaction for the rapid assembly of the carbonate 46, methylenation of 46 and subsequent Claisen rearrangement of the corresponding alkenyl-substituted cyclic ketene acetal to provide the core unsaturated medium-ring lactone 47, and the use of enzyme-mediated acetate deprotection in the presence of a medium-ring lactone.

Natural occurrence, biological activities and synthesis of eight-, nine-, and eleven-membered ring lactones

“…The four total syntheses of octalactins found in the literature, [23][24][25][26] as well as some formal syntheses and related model studies, 27 were exhaustively discussed by Shiina, in his recent review. 5 Therefore, only some aspects of the total synthesis will be briefly depicted here.…”

“…25 The eight-memebred lactone core (27a or 27b) was obtained by Claisen rearrangement of alkenyl-substituted cyclic ketene acetal, generated in situ by selenoxide elimination of the corresponding selenoacetal 25 or by olefination of the corresponding carbonate 26 using dimethyltitanocene (Scheme 6).…”

Métodos de preparação de lactonas de anel médio

“…O rearranjo de ceteno-acetais vinil-e alquenil-substituídos, preparados in situ a partir de fenil seleno-acetais ou de carbonatos, vem sendo bastante explorado na síntese de lactonas de anel mé-dio, pelo grupo de Holmes e Burton [93][94][95][96][97][98] . Em 1997, foi relatada 93 a síntese assimétrica da (+)-laurencina, um éter cíclico de 8 membros.…”

“…A olefinação de carbonatos cíclicos de 6 e 7 membros, promovida pelo dimetiltitanoceno, levou à geração in situ dos respectivos ceteno-acetais, os quais, por sua vez, forneceram lactonas de 8 e 9 membros, através do rearranjo sigmatrópico [3,3] (Esquema 44). Uma aplicação da metodologia acima descrita à síntese das octalactinas A e B foi recentemente descrita pelo grupo 98 . …”

Pyruvate aldolases in chiral carbon–carbon bond formation

“…In addition to managing the flow of small molecules that create and support life, enzymes have found great utility in chemical synthesis [1][2][3] . With the exception of only a few categories, every mechanistic class of reactions known to the organic chemist has an enzymatic equivalent.…”