The objective of this new proposal is to devise a number of total syntheses of complex carbocycles exploiting a novel methodology, that employs chiral dienes ultimately derived from tetronic acids and proline in Diels-Alder (D-A) type reactions. The D-A reaction has become an extension of vinylogous urethane lactone (VUL) enolate carbon-carbon bond formation reactions. As functionally opulent dienes, these systems offer several synthetic advantages relative to other cycloaddition reactions. A major benefit is the formation of a bicyclic ketal, which can function as a protecting group for subsequent synthetic manipulations. These incipient nonracemic cycloadducts permit facile control in the introduction of additional asymmetric centers to the rigid oxa-[2.2.1]- bicyclic heptyl system. The ease of synthesis and accessibility of inexpensive starting materials makes these dienes applicable to large scale asymmetric synthesis. We intend to demonstrate the versatility of these novel dienes within the context of several short enantioselective syntheses of biologically active compounds, while concomitantly studying the origins of their p facial selectivity and expanding their applicability. It is our intent to effect a brief and efficient construction of the antitumor and antimicrobial, esperamicin as the aglycone (24) and several biologically active and distinct pseudo-sugars (50, 34, 43) using this methodology.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM049496-02
Application #
2187045
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1993-04-01
Project End
1996-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Rochester
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627