A Specific Molecular Assembly Procedure

The HMBC data (Table 8-4) confirm the isobutyl structure. An examination of the methyl group protons (T and U) shows HMBC correlations to both C g and C15. In addition, methyl protons T exhibit a connectivity to C20. while the methyl protons U likewise do to C19. Correlations due to Hp are obscured because of the proximity of its signal to those of methyls O and Q. Connectivities, however, are found from the methylene protons N to carbons 18, 19, and 20, thus confirming the presence of the isobutyl group. 

A fourth HMBC correlation is detected between the methylene protons N and the most deshielded carbon. That carbon (Ci) appears to be an ester carbonyl from its chemical shift (8 173.0, Section 3-5c) and exhibits a second connectivity to H. This correlation is crucial because it is the only one that connects Ci indirectly to C9 (via an oxygen as an isovaleryl ester group) of the presumptive cyclohexene fragment. If the connection is confirmed, the molecular fragment 8-1 (with HMBC connectivities shown) accounts for three units of unsaturation and 12 carbons (including the previously surmised carbon-carbon double bond), 17 hydrogens, and 2 oxygens. 

HMBC connectivities between He and C17 and between Hr and C9 also are observed, as are COSY cross peaks between He and Hr. In addition, C9 displays HMBC connectivities to Ha, H[ , and the methyl protons S, while He exhibits HMBC correlations to C4, C5, and C16. 

Since Ha and H also display vicinal coupling, their directly attached carbons (5 and 10) must be adjacent, and confirmatory HMBC connectivities between Ha and C[q and between Hj) and C5 are observed. Furthermore, inspection of the C NMR data indicates that these are the only two noncarbonyl, sp carbons, and it is logical to pair them as C4 and C5. He and Hp each exhibit HMBC connectivities to both carbons 4 and 5, confirming the 4,5-double bond. These data also demonstrate that C5 is located between C4 and Ciq. 

Several COSY and HMBC correlations suggest that methyl 23 be positioned at C4 and that it, in turn, be attached to C9. First, COSY cross peaks between the methyl protons S and Ha and H and HMBC connectivities between (i) the methyl protons S and C4, C5, and C9 and (ii) Ha and methyl C23 argue that methyl 23 be located at C4. Second, these correlations, plus (i) that (COSY) between Ha and He and (ii) those (HMBC) between Ha and C9 and between He and C4, require that C4 be joined to C9. 

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