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Feeding of synthetic precursors to a blocked mutant of 6-deoxyerythronolide B synthase (DEBS) [1] led to production of novel 6-deoxyerythronolide B analogs in vivo containing additional non-natural oxygen substituents as well as additional reactive groups.

Incubation of [6-2H]FPP (14a) with epicubenol synthase isolated from Streptomyces sp. LL-B7 gave epicubenol (1c) labeled at D-9 as established by 2H NMR. These results confirm the involvement of a predicted 1,2-hydride shift in the mechanism of formation of 1.

The sesquiterpenoid microbial metabolite (±)-epicubenol ( 1 ) has been synthesized in 8 steps from a readily available diene aldehyde ( 7 ) using an intramolecular Diels-Alder reaction.

Incorporation of the NAC thioester of (2 S , 3 R )-[3- 2 H, 3- 13 C]-2-methyl-3-hydroxypentanoic acid into both erythromycin A ( 9 ) and B ( 2 ) and nargenicin A 1 ( 3 ) takes place without loss of deuterium.

The sesquiterpene natural product (3R)-nerolidol has been prepared in six steps starting from (3R)linalool.

The absolute configuration of (+)-aristolochene (1a), isolated from Aspergillus terreus, has been established by direct comparison with a sample of (−)-aristolochene (1b) prepared from (+)-valencene (2).

2H NMR analysis of fomannosin (1) derived from [5,5-2H2]-mevalonate established the presence of deuterium at C-5 and C-10, whereas no isotope was located at C-12.

The cyclopentanoid sesquiterpene, cyclonerodiol (l_>, was first isolated by Nozoe from extracts of Trichothecium r0seum.l Subsequently this substance was also found in Gibberella fujikuroi 2,3 and most recently in cultures of Fusarium culmor4 urn. In the latter case cyclonerodiol was accompanied by a related metabolite, cyclonerotriol (2). Nozoe has synthesized cyclonerodio15 by a sequence based primarily on the known Alder ene reaction of linalool. 6,7 The synthesis established the relative configuration of the three ring substituents but gave an epimeric mixture of alcohols at C-6, leaving the relative stereochemistry at this position undetermined. Very recently Hanson has reported a single crystal X-ray analysis of a derivative of cyclonerotriol. 4 Since this latter substance could be correlated with I_,' the study settled the question of the relative stereochemistry at C-6 while confirming Nozoe's earlier conclusions with regard to the ring stereochemistry. We have been studying this problem independently and our results are reported below. To determine the absolute configuration of cyclonerodiol, we chose to degrade i to a pair of known compounds, (-)(2R,3R)-2,3-dimethyl-3-hydroxy cyclopentanone (2) and (-)(1R,2S,3R)-1,2-dimethyl-3-acetyl-cyclopentan-l-ol (4J or their respecttive enantiomers. Both 2 and f have been previously prepared by synthesis from (-)(3R)-linalool.7b'C Initial attempts to effect selective dehydration of the side chain of 1 (3 equiv POC13, pyridine, O", 110 min) gave the known cyclopentene alcohol 2 (45%)1 as the predominant product, accompanied by no more than 10% of isomerit alcohols. While this result precluded direct introduction of a double bond on the side chain, it did suggest that the ring hydroxyl might be preferentially esterified. Indeed, treatment of l_, with 3,5-dinitrobenzoyl chloride (1.5 equiv

Feedings of [1- 13 C]- and [1,2- 13 C 2 ]acetate Aspergillus terreus gave quadrone and terrecyclic acid which were analyzed by 13 C NMR. The pattern of 13 C-enrichments and couplings is consistent with the formation of 1 and 2 by cyclization of farnesyl pyrophosphate.

Feeding of [UL-13C6]-glucose, an in vivo precursor of [1,2-13C2]-acetyl-CoA, gave pentalenolactone in which the pattern of 13C-enrichments and couplings supported a mevalonoid biosynthetic pathway.

Reduction of dehydronerolidol with lithium aluminum hydride in the presence of sodium methoxide gave, in addition to the expected nerolidol, geranyl acetone. Labeling experiments established that the C-1 methyl of geranyl acetone is derived from one of the carbons of the acetylene.

Feeding of [12, 13-13C]-β-trans-bergamotene to cultures of Pseudeurotium ovalis resulted in labeling of C-12 and C-13 of the antibiotic ovalicin, as established by 13 C NMR.

Pentalenolactone E, isolated as the methyl ester from cultures of Streptomyces UC5319, has been to have structure 5.