SYNTHESIS OF DIVERSE TETRAHYDRO-BETA-CARBOLINE-3-CARBOXAMIDES AND TETRAHYDRO-BETA-CARBOLINE-2,3-BIS-LACTAMS ON A VERSATILE 4-HYDROXYTHIOPHENOL-LINKED SOLID SUPPORT

A practical method for solid phase organic synthesis has been develope d using the known, but heretofore underutilized, 4-hydroxythiophenol l inker of Marshall and Liener. The utility of this linker is demonstrat ed by the synthesis of 1,2,3,4-tetrahydro-beta-carboline-3-carboxamide s and -2,3-bis-lactams. Acylation of the resin with L-Boc-tryptophan f ollowed by deprotection and Pictet-Spengler cyclization with a variety of aldehydes provided tetrahydro-beta-carbolines with excellent conve rsion. Cleavage from the resin with primary amines provided the amides and an additional diversity element. Alternatively, acylation at the carboline 2-position with Boc- protected alpha- or beta-amino acid der ivatives followed by deprotection and neutralization resulted in intra molecular cyclization and cleavage to afford 6- and 7-membered bis-lac tams. (C) 1998 Elsevier Science Ltd. All rights reserved.