We have previously demonstrated that the biosynthesis of the C 7 -cyclitol, called valienol (or valienamine), of the ␣-glucosidase inhibitor acarbose starts from the cyclization of sedo-heptulose 7-phosphate to 2-epi-5-epivaliolone (Stratmann, A., Mahmud, T., Lee, S., Distler, J., Thus, a phosphotransferase activity was identified modifying 2-epi-5-epi-valiolone by ATP-dependent phosphorylation. This activity could be attributed to the AcbM protein by verifying this activity in S. lividans strain TK64/pCW4123M, expressing His-tagged AcbM. The Histagged AcbM protein was purified and subsequently characterized as a 2-epi-5-epi-valiolone 7-kinase, presumably catalyzing the first enzyme reaction in the biosynthetic route, leading to an activated form of the intermediate 1-epi-valienol. The AcbK protein could not catalyze the same reaction nor convert any of the other C 7 -cyclitol monomers tested. The 2-epi-5-epi-valiolone 7-phosphate was further converted by the AcbO protein to another isomeric and phosphorylated intermediate, which was likely to be the 2-epimer 5-epi-valiolone 7-phosphate. The products of both enzyme reactions were characterized by mass spectrometric methods. The product of the AcbM-catalyzed reaction, 2-epi-5-epi-valiolone 7-phosphate, was purified on a preparative scale and identified by NMR spectroscopy. A biosynthetic pathway for the pseudodisaccharidic acarviosyl moiety of acarbose is proposed on the basis of these data.

A practical route is decribed for the preparation of the C(7)N core of manumycin-type compounds. Starting from p-benzoquinone, optically pure compounds in both forms can be prepared via enzymatic resolution of a derived diacetoxy conduritol. A diepoxy aminoinositol is accessible which can function for formation of enantiopure epoxyquinones and quinols. Examples are given for acylation reactions of this amine with several acyl derivatives. With this approach (-)-LL-C10037alpha and quinones such as (+)-KT-8110 with 5R,6S-configuration can be synthesized through oxidation. In addition a short route to (+)-bromoxone is described. Most steps include simple epoxide formation and cleavage reactions which all can be carried out in a high stereoselective manner.

Valuable tools for experimental anti‐inflammatory therapy and for clarifying the biological role of neutral sphingomyelinase and ceramide might be represented by manumycins. The antibiotic manumycin A (1), known as a Ras farnesyltransferase inhibitor, and some of its analogues were identified as irreversible inhibitors of neutral sphingomyelinase. The simple analogue 2 is readily accessible, stable and hitherto represents the most potent irreversible inhibitor of neutral sphingomyelinase.

A practical route is described for the flexible preparation of a wide variety of inositol stereoisomers and their polyphosphates. The potential of this approach is demonstrated by the synthesis of myo-, L-chiro-, D-chiro-, epi-, scyllo-, allo-, and neo-inositol systems. Optically pure compounds in either enantiomeric form can be prepared from p-benzoquinone via

In the biosynthesis of the C7-cyclitol moiety, valienol, of the K K-glucosidase inhibitor acarbose in Actinoplanes sp. SE50/110 various cyclitol phosphates, such as 1-epi-valienol-7-phosphate, are postulated precursors. In the cell extracts of Actinoplanes SE50/110 we found a new kinase activity which speci¢cally phosphorylates 1-epi-valienol; other C7-cyclitol analogs were only weakly or not phosphorylated. The puri¢ed product of the kinase reaction turned out to be 1-epi-valienol-7-phosphate in analyses by nuclear magnetic resonance spectroscopy. The enzyme seems not to be encoded by an acb gene and, therefore, plays a role in a salvage pathway rather than directly in the de novo biosynthesis of acarbose.