Joseph P. Marino

Research Interests

The focus of Professor Marino's research group is on the design and development of new synthetic methods and reagents for the efficient assemblage of a wide variety of natural products of medicinal interest. Great emphasis is placed on the design of highly functionalized synthons which incorporate several synthetic operations in one unit and which may ultimately be used for a number of synthetic targets. One of the major thrusts in the area of asymmetric synthesis and involves optically active vinyl sulfoxides. A new type of 3,3-sigmatropic rearrangement has been discovered which involves the reaction of optically active vinyl sulfoxides with haloketenes. This newly discovered process allows for the regioselective and stereoselective formation of functionalized g-butyrolactones. Using this methodology, our group recently completed a total synthesis of optically active podophyllotoxin, which is closely related to the anticancer agent etopside. The vinyl sulfoxide chemistry has also been applied to the synthesis of the indole alkaloid, physostigmine, which has potential for the treatment of Alzheimer's disease. Current applications of this chemistry focus on the aspidosperma alkaloids such as aspidophytine, haplophytine, and aspidospermidine. Generalization of this chemistry involves the use of vinyl sulfilimines in place of sulfoxides.

Another major area of interest is organometallic chemistry involving coupling reactions of activated alkynes and organotellurides, and subsequent transmetalation of the resulting vinyl tellurides to give stereodefined tri- and tetrasubstituted alkenes. This chemistry was used in the total synthesis of Macrolactin A, and is being developed for the synthesis of enediynes and polyene antibiotics such as Inthomycin C.

Selected Publications

• "Total synthesis of (+)-aspidospermidine: A new strategy for the enantiospecific synthesis of aspidosperma alkaloids" Marino J.P., Rubio M.B., Cao G.F., de Dios A. J. Am. Chem. Soc. 2002, 124, 13398.
• "Copper-mediated regioselective allylation and propargylation of 2-(alkylthio)oxazoles" Marino J.P., Nguyen H.N. Tetrahedron Lett. 2003, 44, 7395.
• "Chemoselective syntheses of gamma-butyrolactams using vinyl and sulfilimines and dichloroketene" Marino J.P., Zou N.F. Org. Lett. 2005, 7, 1915.
• "Stereocontrolled Synthesis of (-) Macrolactin A." Marino J.P., McClure M.S., Holub D.P., Comasseto J.V., Tucci F.C. J. Am. Chem. Soc. 2002, 124, 1664.