Methanol → Diazomethane

Participants

Reaction Steps

An aqueous extract (27.5 g) of Ircinia ramosa collected in Australia was fractionated on C4 reversed-phase media, Sephadex LH-20, and C18 HPLC (eluted with a 45-100% gradient of CH3CN in H2O with 0.1% TFA) to give chondropsin A (FIG. 1A, compound (1)) (1 mg) and 73-deoxychondropsin A (5 mg) (FIG. 1A, compound (4)). 73-deoxychondropsin A was obtained as a white powder; [α]D+2.0 (c 0.3, MeOH); UV (MeOH) λmax (log ε) 216 (4.62), 226 (4.61), 261 (4.56) nm; IR νmax (film) 3500-3200, 1660, 1620, 1532, 1204, 1138, 998 cm−1; 1H and 13C NMR, see Table 5; HRFABMS (CsI-doped) obs. [M+Cs]+, m/z 1704.8308, C83H133CsN3O25 requires 1704.8279. HRFABMS established the molecular formula of (4) as C83H133N3O25, which only differed from (1) by a lack of one oxygen atom. The 1H and 13C NMR spectra of (4) (Table 5) were virtually superimposable with those of (1). The only significant spectral differences between the two compounds occurred in a region centered around C-73. It was apparent that the oxymethine at C-73 in (1) was replaced with a methylene in (4). HMBC correlations observed from 11-53 (δ 5.42) and NH-57 (δ 7.62) to C-55 (δ 78.2) confirmed the presence of a C-55 oxymethine group in (4), while an HMBC correlation from H-55 (δ 3.36) to C-73 (δ 40.3) established the position of the new methylene group. A DEPT experiment confirmed that the carbon at δ 40.3 had two attached protons and COSY correlations from H-56 (δ 4.07) to the heavily overlapped region of the H2-73 protons (δ 1.46 and 1.54) were consistent with the presence of a methylene at C-73. Treatment of (4) with diazomethane provided a bis methyl ester derivative (MNa+, m/z 1622.9) (FIG. 1A, compound (5)) and data from a comprehensive set of 2-D NMR experiments with (4) verified that the only difference between (1) and (4) was at C-73.

Provenance & Evidence