C O M M U N I C A T I O N S
yne CE’s as revealed by models (+)-11 and (+)-12. The ene-yne
model (+)-11, with a configuration matching that of phorbasides
at C13, C18, and C19, has a CD spectrum that is almost
superimposable with those of 3a,b, while the mis-matched model
(+)-12 shows a CE with the same sign as that of 3a, but with
diminished magnitude (∆ꢀ +2.7). Thus, CD proVided stereorelay
from C18, C19 to C13, and we may now state the complete
macrolide configuration of 3a,b as (2S,3S,5S,6R,7R,8R,9R,13R,-
18R,19S).
The surprising finding that the configuration of the chlorocy-
clopropane in 3a,b is opposite to that of 4 suggests antipodal ster-
eopreferences in the biosynthesis of the starter unit required for
chain extension by polyketide synthase (PKS) in these analogous
natural products from two different sources. The biosynthetic origin
of chlorocyclopropane rings is presently unknown but may involve
chloride/R-ketoglutarate-dependent “chlorinases” that halogenate an
unactivated CH3 group of the ketide starter units, as in syringomycin
(Streptomyces),10a barbamide (from the cyanobacterium Lyngbya
sp.),10b and the sponge metabolite dysidenin (Dysidea herbacea).11
Since tropical marine sponges often harbor cyanobacteria, it sug-
gests the possibility that phorbasides, and maybe phorboxazoles, are
products of cyanobacteria that live in association with Phorbas sp.
In summary, the complete stereostructures of phorbasides A and
B are assigned aided by semiquantitative analysis of the CD of the
ene-yne chromophore. These findings will be useful for assignments
of other members of the phorbaside-callipeltoside family.
Acknowledgment. The authors thank A. Hoepker and D. Young
(UC Davis) for assistance with synthesis, and P. Searle for initial
separations of Phorbas sp. extract. This work was supported by
NIH grants (CA1225601 and CA85602).
Figure 2. CD spectra in MeOH of phorbaside A (3a, blue solid line) and
phorbaside B (3b, green solid line) with (a) (+)-5a (solid red line) and
(-)-5b (dotted red line); (b) phorbasides, 3a,b and (+)-11 (solid red line)
and (+)-12 (dotted red line); ∆ꢀ for (-)-5b was corrected for enantiomeric
purity.
Scheme 1a
Supporting Information Available: 1H, 13C, 2D NMR data for
phorbasides A and B, tabulated CD values, synthetic procedures, and
characterization of all new compounds. This material is available free
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