Seventeen eudistomins have been isolated from the Caribbean colonial tunicate Eudistoma olivaceum. Twelve are @-carbolines-four of them (eudistomins D, J, N, and 0) unsubstituted at C-I, three (A, B, and M) with pyrrol-2-yl substituents at C-I, and five (G, H, I, P, and Q) with I-pyrrolin-2-yl substituents at C-I; five (eudistomins C, E, F, K, and L) are 1,2,3,4-tetrahydro-@-carbolines with an oxathiazepine ring fused at C-l and N-2. Syntheses are described of eudistomins D, H, I, M, N, 0, and Q and of two related compounds. The major route to both l-(pyrrol-2-yl)- and I-(l-pyrrolin-2-yl)-substituted eudistomins proceeded through Grignard addition of 2-(1,3-dioxa-2-cyclohexyl)ethyl bromide to 1 -cyano-substituted P-carbolines, followed by appropriate cyclization, reduction, and dehydrogenation.Eudistomins A-Q' (1-17, respectively; Chart I) were extracted from the colonial tunicate Eudistoma olivaceum, collected in shallow water in Me~ico, Belize, and Florida. Crude extracts of all the E. olivaceum samples collected inhibited plaque formation by Herpes simplex virus, type 1 (HSV-I), in CV-1 cells (monkey kidney tissue) with little cytotoxicity at the level tested. During the isolation sequence (see Experimental Section and scheme in supplementary material),'a-b E. olivaceum fractions were assayed continuously for antiviral activity, which was found mainly in the chloroform layer, with second and third loci of activity in the I-butanol and toluene layers.Ic Work thus far has centered on the toluene and chloroform layers, from which 17 bioactive @-carbolines have been isolated, some of them with promising antiviral activity; the pyrrolinyl- and pyrrolyl-substituted @-carbolines are least polar, the oxathiazepines next, and the unsubstituted @-carbolines most polar. Structures 1-17 were assigned by spectroscopic techniques (see Tables 1-111 and Figures 1 and 2 in supplementary material),Iasb including high-resolution fast atom bombardment (HRFAB) and HR electron ionization mass spectrometry (EIMS) and 500- and 360-MHz IH and I3C NMR spectroscopy, and by the syntheses of eudistomins D, H, I, M, N, 0, and Q and of two related neoeudistomins, 18and 19 (Chart I), as model compounds.