Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

Abstract

SummaryA unified strategy was followed for the synthesis of three putrescine bisamides, (+)-grandiamide D, dasyclamide and gigantamide A, isolated from leaves of Aglaia gigantea, by making use of a common synthetic intermediate prepared by the Baylis–Hillman reaction. Asymmetric synthesis of the natural (+)-grandiamide D was accomplished from camphor sultam.

Chemoenzymatic Access to (+)-Artabotriol and its Application in Collective Synthesis of (+)-Grandiamide D, (–)-Tulipalin B, (+)-Spirathundiol, and (+)-Artabotriolcaffeate

“…Finally, acid-catalyzed deprotection of a ketal moiety in (+)-diamide 8 furnished the desired natural product (+)-grandiamide D (9) in 77% yield (98% ee by HPLC). The analytical and spectral data obtained for synthetic product was in complete agreement with the reported data for natural product 3,5 and the chemoenzymatic synthesis of (+)-grandiamide D (9) was accomplished in nine steps in 12% overall yield. The natural products (-)-tulipalin B (10) and (+)-spirathundiol (11) have been isolated from Tulipa gesneriana and Spiraea thunbergii Sieb.…”

“…8a Acid-catalyzed hydrolysis of (+)-acetate 2 to the corresponding (+)-alcohol 1 followed by TBDMS-protection provided (-)-silyl ether 3 in 85% yield over two steps. The DIBAL reduction of (-)-diester 3 to the corresponding (+)diol 4 followed by TBAF induced desilylation supplied the desired enantiomerically pure (+)-artabotriol (5) in 67% yield over two steps. The analytical and spectral data obtained for synthetic (+)-artabotriol (5) was in complete agreement with the reported data for natural product (-)artabotriol (5) 2 and the chemoenzymatic first synthesis of (+)-artabotriol (5) was accomplished in five steps in 31% overall yield.…”

“…4 The absolute configuration of (+)-artabotriolcaffeate has been established by using modified Mosher's method. The first total synthesis of (+)-grandiamide D has been recently reported in the literature; 5 although the synthesis of artabotriol is still awaited. Simple retrosynthetic analysis revealed that nature constructs them starting from enantiomerically pure artabotriol in a stepwise fashion via an appropriate sequence of coupling reactions utilizing the naturally occurring putrescine, cinnamic acid, and caffeaic acid.…”

Applications of Morita-Baylis-Hillman Reaction to the Synthesis of Natural Products and Drug Molecules

“…Grandiamide D (324), gigantamide A (328) and dasyclamide (327) were isolated by Duong et al from the leaves of Aglaia gigantean [90]. Very recently Ilangovan and Saravanakumar reported the synthesis of these natural products by using MBH adduct 320 as the common intermediate [91]. They showed that the MBH reaction of ethyl acrylate with aldehyde 318 afforded the racemic adduct 320 which was then converted to the intermediate 323 and dasyclamide 327 via EDCI coupling reaction.…”