Enantioselective total synthesis of callipeltoside A: two approaches to the macrolactone fragment

Abstract

The enantioselective total synthesis of callipeltoside A is described. Two syntheses of the macrolactone subunit are included: the first relies upon an Ireland-Claisen rearrangement to generate the trisubstituted olefin geometry and the second utilizes an enantioselective vinylogous aldol reaction for this purpose. Enantioselective syntheses of the sugar and chlorocyclopropane side chain fragments are also disclosed. The relative and absolute stereochemistry of this natural product was determined by fragment coupling with the two enantiomers of the side chain fragment.

The vinylogous Mukaiyama aldol reaction (VMAR) in natural product synthesis

“…16). 21 A similar concept that takes advantage of a chiral copper catalyst used in combination with a bidentate substrate was put forward by Bolm and co-workers (Fig. 17).…”

“…32, which involves ve main fragments. 21,39 Their synthesis starts with the preparation of aldehyde fragment 104, which can be accessed through an asymmetric VMAR by a chiral Lewis acid catalyst (Fig. 33).…”

The Vinylogous Aldol and Related Addition Reactions: Ten Years of Progress

“…Both macrocyclic structures embody a variable peptide portion Scheme 5. Second Generation Synthesis of (-)-Callipeltoside A (23) 35 Scheme 6. Synthesis of 33, a Macrocyclic Core of (-)-Zampanolide (29) 37 A further couple of cytotoxic natural occurring depsipeptides, Palau'amide (47) and cryptophycin-1 (48), were targeted by Ma and co-workers 41 and Sewald et al, 42 respectively, both exploiting VMAR protocols to assemble the proper polyketide precursor skeletons.…”

“…Complex ent-398 35,194 Chemical Reviews REVIEW This versatile methodology was next extended to involve VMAR additions of silyl dienol ethers derived from ketones, β-diketones, and amides. 202 (2) when the diastereocontrol applied (e.g., eq 2), strict preference for the anticonfigured isomers occurred; (3) the acceptor enantiofacial discrimination was neatly controlled by the chiral catalyst, which was reflected in preference for C5(R)-configured isomers 466 and 468, or C5(S)-isomer 471; and (4) use of morpholinederived dienolates overcame the well-known lethargy involving aliphatic aldehydes, with optimal results obtained in several cases (e.g., eq 3).…”

The Vinylogous Mukaiyama Aldol Reaction in Natural Product Synthesis

“…Accordingly, when the aldol reaction was conducted with 5 mol% of [Cu(O t Bu)((S)-Tol-BINAP)] (from (S)-Tol-BINAP+CuO t Bu), aldol adducts were obtained for a range of aldehydes in yields and enantioselectivities air-stable copper(II) catalyst has been also explored, which activates the aldehyde before addition (Scheme 2.20). This clever strategy was applied in the total synthesis of (−)-callipeltoside A (85) [42]. The vinylogous aldol adduct 84 was generated in very high yield with complete E-selectivity and excellent enantioselectivity (97% ee) under catalysis with the bench-stable dihydrate 83.…”