Complete spectral assignments for the cyclic peptides nordidemnin B and didemnin B, isolated from Trididemnum solidwn, collected at Guadaloupe Island in the Caribbean, are presented. Didemnid tunicates, particulary Lissoclinum palella and Trididemnum solidurn, have proven to be a rich source of novel, biologically active peptides.' The didemnins, fist reported in 1981 by Rinehar?, were isolated from T. solidum collected in the Caribbean and exhibit a wide variety of biological responses including in vitro and in vivo anti-viral, and anticancer activity.' Didemnin B (1) is currently in Phase II clinical trials as a potential new cancer chemotherapeutic agent." Didemnin B also demonstrated impressive immunosuppressive activity in the Simonsen host vs graft assay6 as well as the ability to prolong rat heart allografts in viva.' In 1987, the structure of didemnin B was revised to 2 based on total synthesis" and single crystal x-ray diffraction studies. 9 This revision involved the replacement of the amino acid statine with iso-statine. We now wish to report the structure elucidation of nordidemnin B (3), a lower methylene homologue of 2, and the complete 'H and 13C NMR spectral assignments for both 2 and 3. The two peptides were isolated" from T. solidurn collected at Guadaloupe Island". Preliminary spectral data, including FlIR, 'H and 13C NMR and FABMS, confirmed that one of the metabolites was didemnin B. The second metabolite exhibited very similar spectral data to didemnin B but differed by 14 amu's suggesting the loss of a methyl or methylene group." The close structural relationship between the two peptides, coupled with the absence of detailed 'H and '% NMR assignments for didemnin B in the literature led us to undertake an NMR study of both peptides. The 'H NMR spectrum of didemnin B (2) C,,H,,N,O,, obtained at 500 MHz (CD,) contained three doublet signals above 7.30 ppm which slowly exchanged with D,O indicating their attachment to a heteroatom, the characteristic AB pattern of a tyrosine ammo acid, and 14 methyl bands including one clearly resolved triplet methyl signal, which was part of the iso-statine amino acid. The 13C NMR spectrum obtained at 12.5 MHz contained only 53 distinct signals indicating the presence of four degenerate sets of carbons. Two of these are accounted for by the tyrosine unit. The remaining two were determined by HETCOR13 experiments to be the p and y carbons of the two proline units. DEPT'* and HETCOR experiments established the multiplicities of each carbon and all of the one bond 'H-'C cormlations, respectively. A phase-sensitive, double-quantum-filtered COSY experiment (PSDQF-COSY)" defined the spin systems for all of the amino acid partial structures (2 Pro, N,O-diMeTyr, Thr, Leu, N-Meleu, i-Sta), lactate and hydroxyisovalerylpropionyl (HIP) group, which effectively provided assignments of all the 'H and 'C NMR signals except for the carbonyl and N-methyl carbon signals.
The 'H and "C NMR assignments are summarized in Table 1.
Having established didemnin B as a model, we turned our attention to the new peptide, nordidemnin B (3). The