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Total synthesis of herboxidiene/GEX1A/TAN-1609 has been accomplished in the 22 longest linear sequences starting from 2-butyne-1,4-diol following our recently developed gold-catalyzed Hosomi-Sakurai type of reaction on lactols with allyltrimethyl silane and Stille cross coupling to assemble the advanced fragment. The synthesis of the C10-C19 fragment was accomplished by means of Sharpless epoxidation and asymmetric alkylation reactions starting from (R)-methyl lactate.

The natural herbicide herboxidiene was constructed from two key fragments using a modified Julia olefination based on the benzothiazolyl sulfone activator. Key steps in the synthesis of the C1–C10 oxane fragment were (a) a modified Julia olefination using a 1-phenyl-1H-tetrazolyl sulfone as activator and (b) an intramolecular addition of an alkoxide to an α,β-unsaturated ester. Key steps in the synthesis of the C11–C19 polyketide fragment were (a) a directed aldol reaction using a camphor-10,2-sultam as auxiliary; (b) an Ireland–Claisen rearrangement and (c) a hydroxy-directed epoxidation.

A diastereoselective synthesis of compound 2, which embodies the tetrahydropyranyl core of the polyketide herbicide herboxidiene (1), has been developed using asymmetric epoxidation of nerol as the initial step. Ketone 2 has been elaborated to phosphine oxide 24 which engages in a Horner–Wittig reaction with nonanal to give the E,E-diene 27, an analogue of herboxidiene. However, unlike compound 1, congeners 2 and 27 are not phytotoxic.

The aldehyde 5, corresponding to the C-11 to C-19 fragment of the polyketide herbicide herboxidiene 1, has been prepared in enantio-enriched form.

Nerol 15 is readily converted,via initial asymmetric epoxidation, into compound 2 which contains the tetrahydropyranoid core of herboxidiene 1, a potent phytotoxic compound isolated from Streptomyces sp. A7847.