The Concise Synthesis of a Key Intermediate for the Total Synthesis of Fumagillin­, TNP-470, and Ovalicin

Abstract

The facile synthesis of a key intermediate for the total synthesis of the antiangiogenic compound fumagillin, its semisynthetic analogue TNP-470, and ovalicin is described. The methodology employs a Diels-Alder strategy and a zinc-mediated ring-opening reaction to realize the cyclohexane backbone.

Key words

angiogenesis inhibitors - Diels-Alder reaction - syn reduction - dihydroxylation - HIV

References

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18

Initially, we isolated the double-bond-reduced product with the PMB group intact and then proceeded with PMB deprotection using DDQ in CH₂Cl₂/H₂O. However, a prolonged reaction time with Pd/C also resulted in the saturated PMB-deprotected product.

20

The reaction conditions employed for the attempted protection of the alcohol were (a) TBDPSCl, 1H-imidazole, CH₂Cl₂; (b) MOMCl, DIPEA, CH₂Cl₂; (c) BzCl, py, CH₂Cl₂, and those employed for the attempted ketal deprotection were (a) PTSA (cat.), acetone-H₂O; (b) CSA, acetone-H₂O; (c) PPTS, acetone-H₂O; (d) TMSOTf, CH₂Cl₂.