Enantioselective Total Synthesis of Borrelidin

Abstract

The first total synthesis of the natural product borrelidin is described. The propionate fragment of the molecule was concisely synthesized through catalytic enantioselective reductive aldol reactions, a catalytic Negishi coupling, and a catalytic directed hydrogenation. The propionate segment was then fused to the vinyl iodide fragment through a catalytic Sonogashira coupling. Subsequent catalytic hydrostannylation and catalytic cyanation allowed access to the target structure.

The First Total Synthesis of Phebaclavin A and C

“…This aldehyde was treated with Ph 3 P＝C(CH 2 CH＝CH 2 )-CO 2 Me, 6 followed by solvent-free cyclizing reaction 7 of the resulting ester to afford the 3-allylcoumarin (6a) in over 88% yield. With ample amounts of the key intermediate 6a in hand, oxidative cleavage of 6a was first tried by the osmium tetraoxide catalyzed periodate, 8 but the yield was undesirable. Therefore ozonolysis followed by reduction with dimethyl sulfide of 6a provided aldehyde 7a 9 in 85% yield.…”

Stereoselectivity of Isolated Dehydratase Domains of the Borrelidin Polyketide Synthase: Implications for cis Double Bond Formation

“…Borrelidin (1), an unusual polyketide with potent cytotoxic, anti-angiogenic and anti-malarial activities, contains both a trans and a cis double bond, as confirmed by total synthesis [16][17][18] and X-ray diffraction analysis. [19] Both bor modules 2 (trans double bond) and 3 (cis double bond) contain the expected set of reducing domains (KR and DH) ( Figure 1).…”

Chemoenzymatic Synthesis of the C3–C11‐Fragment of Borrelidin

“…[12] Additionally to fermentation, [9] a variety of synthetic approaches to 1 have been developed [13][14][15][16][17][18] with the first total synthesis reported in 2003 by Morken. [19] Particularly, the stereoselective formation of the polyketide subunit, that is, the C3-C11 fragment in 1, has been intensively investigated. For example, Morken reported a catalytic reductive aldol reaction, Myers' alkylation, Negishi cross-coupling, and catalytic asymmetric hydrogenation as key steps, [19] whereas a sequence of lipase-catalyzed desymmetrization of meso-2,4-dimethyl-1,5-pentanediol, 1,2-addition of lithium acetylide, carboalumination, and catalytic hydrogenation was used by Omura.…”