Synthesis of C9‐C13 and C15‐C21 Subunits of Discodermolide

Abstract

A new synthetic strategy for the construction of two polypropionate subunits of discodermolide, a highly potent anticancer natural product, is reported. The strategy relies on two key reactions: a Shimizu non‐aldol reaction, a stereoselective hydrogenolysis of alkenyl epoxides, to generate the syn hydroxy‐methyl moiety and a NaBH4‐BF3.OEt2 mediated hydride addition reaction. By utilizing this strategy, two different fragments of discodermolide, C9‐C13 subunit and C15‐C21 subunit have been successfully synthesized.

Baeyer–Villiger oxidation: a promising tool for the synthesis of natural products: a review

“…Since several synthetic approaches for this natural compound and its subunits have been reported but in 2020, Si and Kaliappan established the novel non-aldol synthetic strategy for the synthesis of two subunits of (+)-discodermolide by utilizing Baeyer–Villiger oxidation as a key reaction. 112 The synthesis was accomplished with the homologation of alcohol 95 via oxidation in the presence of (COCl) 2 , DMSO, Et 3 N in DCM followed by Wittig reaction and reduction to afford an allylic alcohol 96 in 88%. In the next step, the alcohol 96 underwent Baeyer–Villiger oxidation with m -CPBA to generate an epoxy alcohol 97 in 14 : 1 diastereomeric ratio with 82% yield.…”

Expeditious Asymmetric Synthesis of Polypropionates Relying on Sulfur Dioxide-Induced C–C Bond Forming Reactions

“…The stereoselective construction of all possible stereoisomers of stereotriads R 3 CH(Me)-CH(OH)-CH(Me)-R 4 (6, Figure 2) has been achieved by many methods [29] including those based on aldol or crotylation reactions of an aldehyde or its metallic enolate analogue bearing an α-methyl substituent [30][31][32][33][34][35][36]. Non-aldol formation of stereotriads has been proposed, such as the Sharpless asymmetric epoxidation of allyl alcohol followed by Pd-catalyzed hydrogenolysis of alkenyl Non-aldol formation of stereotriads has been proposed, such as the Sharpless asymmetric epoxidation of allyl alcohol followed by Pd-catalyzed hydrogenolysis of alkenyl oxirane with HCOOH [37,38] and the cuprate addition to epoxides [39][40][41]. A method applying an intramolecular Rh-catalyzed silylformylation/crotylsilylation/"aprotic" Tamao oxidation sequence has been developed by Leighton and co-workers [42][43][44].…”