The total synthesis of the tunicate metabolite mandelalide A and the correction of its originally assigned stereochemistry are reported. Key features of the convergent, fully stereocontrolled route include the use of a Prins cyclization for the diastereoselective construction of the tetrahydropyran subunit, Rychnovsky-Bartlett cyclization for the preparation of the tetrahydrofuran moiety, Suzuki coupling, Horner-Wadsworth-Emmons macrocyclization, and glycosylation to append the L-rhamnose-derived pyranoside.

Sialosides incorporating substituted amides or amines at 9-position of sialic acid moiety have been synthesized and evaluated as CD22 inhibitors. Several derivatives exhibited inhibitory potency in sub- to low micromolar range (e. g., 8o, 9d, 9g, and 9k showed IC 50 values 0.40, 0.47, 0.24, and 0.23 microM, respectively, for hCD22, while 8p, 8q, and 9f, showed IC 50 values 1.70, 2.90, and 4.10 microM, respectively, for mCD22). The most significant result was the strongly enhanced affinity of 9g and 9k containing 9-(2' or 4'-hydroxy-4-biphenyl) methylamino substituents (600-fold more potent for hCD22 than the corresponding 9-hydroxy derivative; 7a). Molecular modeling study was carried out to get some insights into the molecular basis of CD22 inhibition. To the best of our knowledge, this is the first systematic structure-affinity relationship study on inhibition of CD22.

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Highly reducing polyketide synthases (HR-PKSs) produce structurally diverse polyketides (PKs). The PK diversity is constructed by av ariety of factors,i ncluding the b-keto processing,c hain length, methylation pattern, and relative and absolute configurations of the substituents.W e examined the stereochemical course of the PK processing for the synthesis of polyhydroxyPKs such as phialotides,phomenoic acid, and ACR-toxin. Heterologous expression of aH R-PKS gene,atrans-acting enoylreductase gene,and atruncated non-ribosomal peptide synthetase gene resulted in the formation of al inear PK with multiple stereogenic centers.T he absolute configurations of the stereogenic centers were determined by chemical degradation followed by comparison of the degradation products with synthetic standards.As tereochemical rule was proposed to explain the absolute configurations of other reduced PKs and highlights an error in the absolute configurations of ar eported structure.T he present work demonstrates that focused functional analysis of functionally related HR-PKSs leads to ab etter understanding of the stereochemical course.

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We wish to report studies of excited-state electron transfer involving monolayer quantities of electrode-confined Re carbonyl complexes la or 2a with the aim of developing approaches to molecule-based photoelectrochemical devices. Surfaces derivatized with l a or 2a have been characterized with respect to electrochemical, photophysical, and spectroscopic properties and compared to solution analogues lb and 2b. Photoelectrochemical l a , R = n-pr-Sic13 1 b, R = allyl Za, R = n-pr-SiCl3 Zb, R = allyl experiments show that sustained photooxidation of the sacrificial reagent triethanolamine, TEA, can be brought about as shown in part a or part b of Scheme I.Possible applications to energy conversion are often cited to explain interest in excited-state electron transfer in muhicomponent molecules. While reports of the synthesis and characterization of multicomponent molecules are abundant, reports concerning the application of such molecules to the energy conversion problem are scarce. The well characterized twocomponent molecule 2a provides a good system to investigate the viability of a simple multicomponent molecular system in optical energy conversion and provides an important starting point from which more efficient systems can be designed.Our overall aim is to generate an organized electrode-confined molecular assembly that achieves vectorial electron transfer as a result of light absorption. Efforts to mimic the mechanism of charge separation in natural photosynthetic systems have resulted in the synthesis and study of numerous multicomponent m0lecules.~-5 A porphyrin-containing molecular pentad provides a striking example of a synthetic multicomponent molecule that efficiently yields a charge-separated state with a lifetime of 55 Address correspondence to this author. ( I ) (a) Gust, D.; Moore, T. A., Eds. Covalently Linked Donor-Acceptor Species for Mimicry of Photosynthetic Electron and Energy Transfer. Terruhedron 1989,45 (IS), 4669. (b) Gust, D.; Moore, T. A. Science 1989, 244, 35, and references therein. ( 2 ) McMahon, R. J.; Force, K. R.; Patterson, H. H.; Wrighton, M. S. J.

We theoretically investigate field-free molecular orientation by using an off-resonant two-color shaped laser pulse with a slow turn-on and rapid turn-off and a time-delayed THz laser pulse. It is shown that the molecular orientation can be greatly enhanced by applying this scheme compared to the two-color shaped or THz laser pulse alone. We discuss the effects of the rise time and the electric field amplitude of the two-color shaped laser pulse on molecular orientation, and demonstrate that effective molecular orientation can be achieved by a moderate intensity laser pulse with a short rise time. Furthermore, by changing the delay time between the two-color shaped laser pulse and the THz laser pulse and the carrier envelope phase of the THz laser pulse, the molecular orientation can be enhanced or lowered to some degree.