A-Lipomycin

Me glycosides are components of the antibiotic a-lipomycin produced by Streptomyces aureofaciens. A common constit. of plant glycosides, e.g. Digitoxin. Found, inter alia, in the Cruciferae, Scrophulariaceae, Asclepiadaceae and Apocynaceae. 

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. 

The specific rotation of the specimen of (55,12 / ,13 5)-7 just described was -237 under the same conditions that Zeeck et al. had found the specific rotation of natural a-lipomycin (8) to be -229. We considered these values as identical. All indications, hence, were that the stereoformula of natural a-lipomycin is (55,12 / ,13 5)-7. It was certainly a good reason for having a bottle of champagne. 

SCHEME 14 Accomplishing the synthesis of our only a-lipomycin candidate by a tandem coupling involving distannane 18 and the iodoalkene glycoside 32 ( sugar-containing eastern building block ). Juxtaposition of the specific rotation of our synthetic material and of natural a-lipomycin as reported by Zeeck et al. an excellent match once moie ... 

The message that we took from the preceding paragraph was that we needed to further assure ourselves of the stereostracture of the newly assigned stereocenters of the lipomycins by an independent approach the isolation of natural a-lipomycin (7), its hydrolysis to p-lipomycin (8), the excision of the substructure with the stereocenters in question, and the assignment of their stereostructures by HPLC or GLC comparisons with stereodefined reference compounds. 

We isolated a-lipomycin (7) from S. aureofaciens (Tii 117) under the auspices of Elisabeth Welle. She is a biologist from the group of Professor Bechthold, our colleague from the Pharmacy Department of our university. She was a member and he was the leader of the team that identified the gene cluster encoding the biosynthesis of the lipomycins. We first reanimated Bechthold s strain of S. aureofaciens. It had been dormant for several years due to having been stored in deep freezers After it regained vitality it was... 

SCHEME 15 Our isolation of the natural products a-lipomycin (7) and P-Upomycin (8) from Streptomyces aureofaciens and its scale. ... 

Altogether, we developed a new western building block for synthesizing poly-enoyltetramic acids. We demonstrated its usefulness in accomplishing total syntheses of the polyenoyltetramic acid natural products a-lipomycin (7) and p-lipomycin (8). We identified the configurations of the previously unassigned stereocenters of both compounds as AR and 155. We might have considered these deductions reasonably safe. However, we preferred absolute... 

Cordycepin (3 -deoxyadenosine) has been shown to inhibit the synthesis of proteins in germinating cotton cotyledons, whereas 3 -deoxycytidine did not. The methanolysis of a-lipomycin to give 2,6-dideoxyhexose derivatives is mentioned in Chapter 3. 

---