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Monday, November 30, 2009
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Crispine A (Zhou), Cermizine C (Zhang), Tangutorine (Poupon), FR901483 (Kerr), Serratezomine A (Johnston)

Enantioselective hydrogenation of enamides is a well-established transformation. The corresponding reduction of enamines has been elusive. Qi-Lin Zhou of Nankai University designed (J. Am. Chem. Soc. 2009, 131, 1366. ) an Ir catalyst that reduced 2 to the Carpus alkaloid Crispine A (3) in high ee.

Direct conversion of C-H to C-C bonds is a powerful synthetic transformation. Liming Zhang, now at the University of California, Santa Barbara, observed (J. Am. Chem. Soc. 2009, 131, 8394. ) that a gold catalyst converted the N-oxide of 4 into 5, that was then deoxygenated to give Cermizine C (6). The gold catalyst and the N-oxide combined to convert the alkyne into an α-keto carbene, in the process reducing the N-oxide back to the amine. The carbene then abstracted a hydride from the carbon adjacent to the amine, generating an intermediate that collapsed to give 5 with high diastereocontrol.

Tangutorine (10), isolated from the leaves of Nitraria tangutorum, affects the morphology of human colon cancer cells. In a biomimetic approach, Erwan Poupon of the Université Paris-Sud stirred (Org. Lett. 2009, 11, 1891. ) glutaraldehyde (7) with bicarbonate to give an unstable carbocyclic dimer. Addition of tryptamine in acetic acid delivered the pentacyclic product 9, that was reduced with borohydride to give the crystalline Tangutorine (10).

FR901483, a potent immunosuppressive isolated from a Cladobotyrum fermentation broth, presents an challenging array of stereogenic centers in its tricyclic skeleton. Michael A. Kerr of the University of Western Ontario prepared (Org. Lett. 2009, 11, 777. ) the activated cyclopropane 11, then effected intramolecular dipolar opening with an intermediate imine, yielding the tricyclic 12.

The Lycopodium alkaloid Serratezomine A (21) presents a similarly challenging array of stereogenic centers in its tetracyclic structure. Jeffrey N. Johnston of Vanderbilt University constructed (J. Am. Chem. Soc. 2009, 131, 3470. ) the pyrrolidine ring of 15 using the imine free radical acceptor that he had previously developed. Having the alkene-Sn bond in place then enabled coupling with the acid chloride 16. Oxidative deprotection of 17 freed the enamine, that added in a conjugate sense to the unsaturated ester, kinetically setting the axial branch of 18. A second CAN-mediated step, allylation with 19, set the quaternary center of Serratezomine A (21).

D. F. Taber, Org. Chem. Highlights 2009, November 30.
URL: https://www.organic-chemistry.org/Highlights/2009/30November.shtm