A novel synthesis of a nine-membered ring

Elucidation of the Biosynthetic Pathway Leading to the Complex Nonadride Phomoidride B

“…11 Later, a biomimetic synthesis of 12-epi-glaucanic acid was achieved by Sutherland via treatment of a DMF solution of anhydride 5 with triethylamine to afford 8. [12][13][14] Although the dimerization product 8 was obtained in only a 4% yield, the outcome nonetheless provided further evidence supporting a dimerization biosynthetic pathway for the nonadrides.…”

“…This result demonstrates that the absolute position as well as the relative relationship of the label was conserved (i.e. the 13 C-13 C bond in the original acetate feeding unit remained intact throughout the whole metabolic pathway) leaving little doubt about the postulated polyketide synthase or fatty acid synthase origin of this part of the phomoidride molecule. The 13 C feeding studies depicted above unequivocally establish the biosynthetic origin of the entire carbon scaffold of the phomoidride B molecule.…”

“…Our original experiment using twice this incubation time resulted in uniform 13 C-labeling of phomoidride B, presumably due to catabolism and redistribution of the labeled material. This curious occurrence allowed us to verify the C-C connectivity of the molecule by direct observation of the 13 C- 13 C COSY spectrum of phomoidride B and to discover a minor misassignment of the resonances corresponding to the olefinic side chain carbons in the original structure elucidation paper (C2 and C3 assignments were reversed, as well as C23 and C24). The complementary experiment using [1,4-13 C 2 ]-succinate resulted in significant enhancement of the corresponding carboxyl carbons (C27, C29, and C30) in the phomoidride B molecule, supporting their introduction from exogenously labeled succinate ( Figure 4).…”

“…When [2-13 C]-N,S-diacetyl cysteamine was fed to the culture, no intensity enhancement was immediately detectable for any of the carbons in the phomoidride B molecule by simple visual inspection of the corresponding resonances in the 13 C NMR spectrum. 27 However, internal normalization of the peak intensities, followed by quantitative comparison with the corresponding normalized peak intensities in the 13 C NMR spectrum for the unenriched phomoidride B according to the method of Hanson and co-workers was performed. 28,29 A graphical representation of this result ( Figure 5) clearly illustrated the expected alternating pattern which is the signature of a polyketide or fatty acid synthase biosynthetic pathway.…”

Biomimetic Synthesis of Non‐Aromatic Polycyclic Polyketides

“…The reaction via an endo transition state would give the correct relative stereochemistry. This dimerization was attempted in vitro by treating anhydride 1 with triethylamine in dimethylformamide (DMF) [9b, 10]. Yet it only gave 4% of the epimeric exo product, iso-glaucanic acid (3).…”