Enantioselective Total Synthesis of Octalactin A Using Asymmetric Aldol Reactions and a Rapid Lactonization To Form a Medium‐Sized Ring

Abstract

Octalactin A, an antitumor agent containing an eight-membered lactone moiety, has been stereoselectively prepared by means of enantioselective aldol reactions of selected silyl enolates with achiral aldehydes, promoted by a chiral Sn(II) complex. The medium-sized lactone part was effectively constructed by way of a new and rapid mixed-anhydride lactonization using 2-methyl-6-nitrobenzoic anhydride (MNBA) with a catalytic amount of 4-(dimethylamino)pyridine (DMAP) or 4-(dimethylamino)pyridine 1-oxide (DMAPO). The use of only 5 mol % of DMAP or 2 mol % of DMAPO rapidly promoted formation of the medium-sized ring of the octalactin, demonstrating the remarkable efficiency of the new lactonization protocol.

Transition metals in organic synthesis: Highlights for the year 2005

“…Hydrozirconation of terminal alkynes followed by addition of iodine or NBS to produce alkenyl iodides or bromides were used in synthetic applications toward latrunculin A [108], (+)-apiosporamide [127], octalactin A [1488], (4E,6Z,10Z)-4,6,10-hexadecatrien-1-ol [331], lobatamide analogs [52], pyranicin [340], toward (+)-sorangicin [268] and the C10-C24 fragment of inostamycins [253]. Regioselective hydrozirconation of an internal alkyne followed by iodine quench was used in a synthesis of spirofungins [228].…”

Metathetic Synthesis of Common and Medium-Sized Lactones: The State of the Art

“…The RCM reactions were performed using the first-generation catalyst G1, in the absence of Lewis acid cocatalysts or of additional cyclic or conformational constraints in the diene 143 (Scheme 48) [208]. The yields of the eight-membered δ,ε-unsaturated lactone 144 and its various epimers (20-90%) are remarkable in consideration of the inherent difficulty of formation of such rings and are comparable to those based on a mixed-anhydride lactonization procedure affording the corresponding saturated ring systems [209].…”

Stereoselective Acetate Aldol Reactions

“…The power of this methodology was demonstrated on the addition of 36a to chiral α-OTBS aldehydes (98) and (ent-98), in which the C3 stereocenter of aldols (99) and (100) was controlled by the diamine (96) regardless of the inherent diastereofacial preference of the chiral aldehydes (Scheme 1.35) [73,74].…”