Martins Total Synthesis of Manzamine

Having now secured the most challenging structural element of this fragment, the Boc protecting group in 63 was then removed upon treatment with TMSOTf in the presence of 2,6-lutidine, with subsequent exposure to p-TsOH in MeOH completing the synthesis 

Up to this point, the overall sequence had proceeded with few major synthetic hurdles which proved unyielding to sufficient experimentation. Unfortunately, this pattern was about to be broken. Despite the ease with which the 8-membered azocene E-ring was fashioned by metathesis in model studies related to the manzamine problem, the conversion of 29 into 72 occurred under optimized conditions (110 mol% of 70, 0.004 m in C Hg, A, 30 minutes) in a modest yield of only 26 %, with the final product isolated after acid-catalyzed removal of the dimethyl acetal protecting group. This result is likely the product of alternative metathesis pathways available due to the proximal olefin in the 13-member D-ring and not some other inherent polar functional group in the test substrate. Indeed, protection of the free hydroxy group as well as 

During a 1965 lecture describing a successful total synthesis of the natural product colchicine, R. B. Woodward eloquently formulated the fundamental appeal of endeavors in total synthesis when he noted that 

Kobayashi, Y. Ohizumi, Y. Tomotake, T. Matsuzaki, Y. Hirata, Tetrahedron Lett. 1987, 28, 621. 

A modified form of the Baldwin-Whitehead hypo- 7. thesis has also been proposed to explain the origins 

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