Vinylogous amide photochemistry. Synthesis of the pentacyclic core of manzamine A

John Eugene Stelmach, University of Pennsylvania


This dissertation describes the application of the vinylogous amide (2+2) photocycloaddition/Mannich fragmentation/Mannich closure cascade (54 to 58) to the synthesis of the pentacyclic nucleus of the anti-leukemic marine alkaloid manzamine A (78). Two key transformations for the synthesis of manzamine pentacycle (200) were investigated: the transannular photocycloaddition of an 18-membered vinylogous amide (203 to 200) and intramolecular photocycloaddition of 256 followed by 13-membered ring formation. The desired transannular photocycloaddition of the 18-membered vinylogous amide 203 and of structurally simplified model 18- and 20-membered vinylogous amides was not observed. The failure of the macrocyclic substrates to undergo the desired transannular photocycloaddition was attributed to an unfavorable macrocycle conformation. Intramolecular photocycloaddition of 256 followed by 13-membered ring formation readily afforded the pentacycle 200. However, in the case where R was an unprotected hydroxyl, attempted 13-membered ring formation led to a rearrangement product derived from a retro-Michael elimination of the 5-membered ring nitrogen. The stereoselectivity of the intramolecular photocycloaddition depends on the R substituent. If R of 256 is a trans-alcohol the major diasteromer obtained in the intramolecular photocycloaddition has the relative stereochemistry of Manzamine A. However, the present synthetic route to trans-alcohol photosubstrates is inadequate. In order to obtained trans-alcohol photosubstrates the homochiral oxazolidone 452 was prepared in good yield via a short synthetic route from 449a. The use of oxazolidone 452 for the synthesis of homochiral photosubstrates which possess R trans-alcohol substituent is currently under investigation.$\sp*$ ftn$\sp*$Please refer to the dissertation for diagrams

Subject Area

Organic chemistry

Recommended Citation

Stelmach, John Eugene, "Vinylogous amide photochemistry. Synthesis of the pentacyclic core of manzamine A" (1996). Dissertations available from ProQuest. AAI9628010.