Total Synthesis and Stereochemical Assignment of Penicitide A

Abstract

Stereoselective total synthesis of marine secondary metabolite penicitide A has been accomplished for the first time following a convergent approach. The salient feature of this study includes Horner–Wadsworth–Emmons (HWE) olefination, Evans methylations, Crimmins acetate aldol reaction, and cross olefin metathesis. Our synthetic study established the stereochemistry of unassigned C-10 and C-12 centers and also disclosed the absolute configurations of C-3 and C-5 stereocenters.

Marine natural products

“…Total synthesis of the proposed structure of chaunopyran A implied that revision of the absolute configuration to 786 is required, 281 whilst total synthesis of penicitide A both revised the previous partial stereochemical assignment and established the absolute configuration as 787 . 282 Convergent and biomimetic syntheses of penicimutanin A, penicimutanolone and penicimutatin established the absolute configurations as 788–790 respectively 283 and syntheses of peribysins A–C and F–G revised the stereochemistry of peribysins A, C, F and G (to 791–794 respectively) and represented the first syntheses of peribysins C, F and G. 284 Six step syntheses of the proposed and revised structures of (−)-versiquinazoline H led to correction of stereochemistry and the assignment of the absolute configuration as 795 . 285 Synthesis of (−)-curvulamine C has been achieved from commercially available starting materials 286 and its yield from the producing fungus has been improved through addition of precursors alanine and proline to the culture.…”

Stereoselective Synthesis of Acyclic Skeleton of Boscartin A

“…IBX (entry 4) was found as the best to get the corresponding α,β-unsaturated ketone with 75% yield which was reduced further by BH 3 –DMS in the presence of ( S )-CBS 9 to yield the required epoxy alcohol 11 along with its corresponding minor counterpart ( dr = 5:1) which were separated by silica gel column chromatography. Stereochemistry of the newly generated hydroxy center of epoxy alcohol 11 was confirmed as ( R ) by modified ­Mosher’s ester analysis 10 by synthesizing esters 25a and 25b from alcohol 11 in the presence of 2,4,6-trichlorobenzoyl chloride/Et 3 N/DMAP following the Yamaguchi protocol 11 4b (Scheme 4 ).…”

Synthesis of the Key Skeleton of Phosphoeleganin

“…The synthesis of key skeleton of phosphoeleganin is shown in Scheme 4 . The mixture of alcohols 7 was oxidized under Swern conditions 5e g h , 14 and then treated with sulfone 6 in the presence of NaHMDS by following a Julia–­Kocienski olefination protocol 5b f g , 11 to give a mixture of alkenes 24 in 75% yield (over two steps). It is important to mention that we did not pay attention to the separation of those olefins of similar polarities, even in the advanced stages, as a hydrogenation at a later stage would provide a single compound.…”