P-Lipomycin

FIG. 3 The polyenoyltetramic acid antibiotic a-lipomycin (7) and its aglycon P-lipomycin (8). The (stereo)structures of these compounds are depicted as formulated before our syntheses were accomplished. How the information shown here was gained is detailed in Section 3.1. The asterisks designate stereocenters with previously unknown configurations. 

Our "Never-Change-a-Winning-Team"-Type Retrosynthetic Analysis of a- and P-Lipomycin... 

Our eastern budding blocks were required in the plural form (Fig. 6). We needed all stereoisomeric iodoalkenes 32 either unprotected—i.e., with R = H (which was fine, as it would turn out)—or with a mildly removable protecting group R H (Fig. 11). These four eastern building blocks would be converted into the four p-lipomycin candidates. One of them would equal the natural product (8 cf. Fig. 6). Our fifth eastern building block was the naturally configured iodoalkene 32 equipped with R=p-D-digitoxyl or with a protected form thereof. This compound would precede our totally synthetic ot-lipomycin (7 cf. Fig. 6). 

The other p-lipomycin isomers were prepared in the same manner specified for the isomer (5S,12 / ,13 S )-8 in Scheme 13. Fig. 12 compiles the ensemble of these four molecules including their stereostructures and specific... 

SCHEME 13 Representative example of how we con leted our four p-liptandem couplings involving die lincl in distannane 18 and our library of stereochemically varied iodoalkenes 32 ( sugar-free eastern building blocks ). One sees qiecifically the synthesis of what would turn out to equal natural p-lipomycin. 

FIG. 12 Juxtaposition of the specific rotations of our synthetic materials and the specimen of naturally occurring P-lipomycin reported by Zeeck et a very... 

The structures of the final products of our syntheses were indisputable. Yet their pairwise identities with the structures of a- and p-lipomycin, respectively, were perhaps not altogether indisputable. This qualification, of course, is a euphemism for disputable —an ugly notion in a field as exacting as science. Clearly, in real life, it is advisable to think twice before stating mission accomplished aloud. As scientists we have been trained to be extra careful. Accordingly, many of us tend to exercise more prudent judgments in our role as research team leaders than others do in their role as, for example, state leaders (politicians ). 

Last isolated intermediate- -(2 S,14R,15S)-98 — en route to synthetic p-lipomycin ... 

FIG. 13 The teimmating steps of our surmised total synthesis of naturally configured P-lipomycin provided compounds (cf. Scheme 13), which we could not safely designate as NMR-pure. ... 

Outside the Confinements of a Synthetic Laboratory Isolating a- and P-Lipomycin from 5. aureofaciens... 

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