Total synthesis of Class II and Class III Galbulimima Alkaloids

I. Total Synthesis of All Class III Galbulimima Alkaloids We describe the total synthesis of (+)- and (-)-galbulimima alkaloid 13, (-)-himgaline anad (-)-himbadine. The absolute stereochemistry of natural (-)-galbulimima alkaloid 13 is revised to 2S. Sequential use of catalytic cross-coupling and cross-metathesis reactions followed by an intramolecular Diels-Alder reaction provided the required trans-decalin AB-ring system and masked the Cl 6-carbonyl as an N-vinyl carbamate for late stage unveiling in the form of the necessary C16-enone. A vinyl-radical cyclization secured the C-ring while successful execution of our strategy for introduction of the CDE-ring system in complex galbulimima alkaloids provided the target pentacycle with complete diastereoselection. II. Total Synthesis of (-)-Himandrine We describe the first total synthesis of (-)-himandrine, a member of the class II galbulimima alkaloids. Noteworthy features of this chemistry include a diastereoselective Diels- Alder reaction in the rapid synthesis of the tricycle ABC-ring system in enantiomerically enriched form, the use of a formal [3+3] annulation strategy to secure the CDE-ring system with complete diastereoselection, and successful implementation of our biogenetically inspired oxidative spirocyclization of an advanced intermediate. The successful and direct late-stage formation of the F-ring in the hexacyclic core of himandrine drew on the power of biogenetic considerations and fully utilized the inherent chemistry of a plausible biosynthetic intermediate.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2010

Author dc:creator

• Tjandra, Meiliana

Advisor dc:contributor.advisor

• Mohammad Movassaghi.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/64583

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/64583