Kulokekahilide-1, a Cytotoxic Depsipeptide from the Cephalaspidean Mollusk Philinopsis speciosa

Abstract

The cytotoxic depsipeptide kulokekahilide-1, which contains two unusual amino acids, 4-phenylvaline and 3-amino-2-methylhexanoic acid, was isolated from the cephalaspidean mollusk Philinopsis speciosa. Structure elucidation of kulokekahilide-1 was carried out by spectroscopic analysis and chemical degradation. The absolute stereochemistry was determined by Marfey analysis for amino acids and chiral HPLC analysis for hydroxy acids. All four stereoisomers of 4-phenylvaline and 3-amino-2-methylhexanoic acid, which were necessary for Marfey analysis, were synthesized by use of the Heck reaction and Evans's method, respectively. Kulokekahilide-1 showed cytotoxicity against P388 murine leukemia cells with an IC(50) value of 2.1 microg/mL.

Carriebowmide, a New Cyclodepsipeptide from the Marine Cyanobacterium Lyngbya polychroa

“…2957, 2870, 1738, 1650, 1646, 1538, 1453, 1410, 1385, 1367, 1315, 1279, 1240, 1215, 1186, 1083 cm -1 ; 1 H and 13 C NMR data, see Table 1, assignments were made by interpretation of 2D DQF COSY, edited- Advanced Marfey Analysis. 6 A portion of the acid hydrolysate (0.05 mg) and the standards (2R,3R)-Amha and (2S,3R)-Amha were separately derivatized by treatment with 1 M NaHCO3 (50 µL) and a 1% solution of 1-fluoro-2,4-dinitrophenyl-5-L-alaninamide in acetone (50 µL). After heating at 45°C for 1 h, the reaction mixtures were cooled, acidified with 2 N HCL (25 µL), and diluted with MeCN (100 µL).…”

“…The existence of the uncommon 2-hydroxy-3-methylbutyric acid (Hmba) moiety was revealed by the presence of a broad signal (δ H 5.15, δ C 76.0) corresponding to an R-hydroxymethine proton. 6 The expected cross-peak observed in the COSY spectrum for vicinal coupling between H-47 and H-48 was relatively weak and seen only at the noise level. The small coupling constant of H-47 and the high multiplicity of H-48 contribute to the weak cross-peak seen in the COSY spectrum.…”

β‐Amino Acid Biosynthesis

“…Amha (123) occurs in depsipeptides such as guineamide D (135) [132], kulokekahilide-1 [138], malevamide B [139], and the ulongamides A-F [140]. Aoya (124) has been found as constituent of dolastatin 17 (136) [141], and Amoa (125) in guineamide C (137) [132], malevamide C [139], onchidin [142], and ulongapeptin [143] (Figure 4.20).…”

Toward the Total Synthesis of Onchidin, a Cytotoxic Cyclic Depsipeptide from a Mollusc

“…It was found that this type of a-methyl-bamino acid is a crucial component of many biologically active cyclic peptides of marine origin. Representative examples are nodularin [3] and microcystin, [4] which are notorious for their hepatotoxicity, and majusculA C H T U N G T R E N N U N G amide C, [5] dolastatin 11 and 12, [6] and kulokekahilide-1, [7] which are valued for their antifungal and antineoplastic activity.…”