Abstract
Eudistomins (1) have been isolated from colonial tunicates and display antiviral activity. We have synthesized these eudistomins which established the absolute configuration. Reaction of N-hydroxytryptamines (2) and protected L-cysteinals (3) gave optically active nitrones (4) in good yields (Table I). When 4 (R_1=H) was treated with TFA-CH_2Cl_2 at room temperature for a few mins, the tetracyclic compounds (5) were obtained as the major product along with the β-carbolines (6) (Table II). The β-carbolines (6) were obtained as the sole product with high selectivity for 6β when the reaction was carried out at ?78℃. In contrast, 4 (R_1=Me) gave the corresponding tetracycles 5 regardless of the reaction temperature and noβ-carboline was obtained. The tetracyclic compound (R1=H) can be transformed to the correspondingβ-carboline with TFA-CH-2Cl_2. Theβ-carboline (6aβ, 6eβ) was cyclized with NCS-CCl_4 to give the desired oxathiazepine (9b, 4%). As an improved cyclization, the reaction of the sulfoxide (10a) with TsOH gave the oxathiazepine (9a) in 21% yield. The enantiomer of debromoeudistomin L (1a) was obtained by deprotection of 9b. The nitrone obtained from 2a and D-cysteinal gave the natural (-)-1a by the similar reactions. On the other hand, the bromination of the tetracyclic compound (5e) gave the bromo derivative (14) selectively. Ring transformation of 14 with TFA gave theβ-carboline (24α), which was further converted to (-)-eudistomin L (1b) by analogous reactions. Other eudistomins (1e, 1f) have also been synthesized by the similar reaction of D-cysteinals with 6-bromo-, and 6-bromo-5-methoxy-N-hydroxytryptamines, respectively.
