A highly regio- and diastereoselective TiCl4-mediated vinylogous Mukaiyama aldol reaction using the chiral vinylketene silyl N,O-acetal has been developed. The present vinylogous Mukaiyama aldol reaction provides a unique and effective means of controlling remote asymmetric induction. The methyl group at the alpha-position is important in achieving a high level of stereoselectivity. From a synthetic point of view, this methodology can provide a one-step construction of delta-hydroxy-alpha,gamma-dimethyl-alpha,beta-unsaturated carbonyl unit that is seen in many natural polyketide products.

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The total synthesis of cytotoxic marine natural products possessing tubulin polymerization and microtubule stabilization properties, sarcodictyins A (7) and B (8), is described. Two related approaches to these target molecules have been developed, both utilizing (+)-carvone (9) as starting material. The first approach involves a stereoselective construction of acetylenic aldehyde 27 (Scheme 2) while the second approach proceeds through a more direct but less selective sequence to the similar intermediate 36 (Scheme 3). Both strategies involve ring closures of the acetylenic aldehyde precursors to 10-membered rings under basic conditions followed by elaboration and selective reduction of the acetylenic linkage to a cis double bond. This promotes bridging to form the required tricyclic skeleton of the sarcodictyins (27 f 37 f 38 f 39 f 4, Scheme 4 and 37 f 44 f 45 f 46 f 47 f 42, Scheme 5) and (36 f 48 f 45, Scheme 6). Installation of the (E)-N(6′)-methylurocanic acid residue was achieved by esterification with mixed anhydride 52, while the C-3 ester moieties were installed by standard deprotection, oxidation, and esterification procedures.

The total synthesis of the cytotoxic marine natural products eleutherobin (1) and eleuthosides A (2) and B (3) is described. The strategy involves glycosidation of the (+)-carvone-derived intermediate 7 with the arabinose-derived trichloroacetimidate 9 followed by base-induced ring closure and elaboration to afford the dihydroxy eneynone 19. Selective hydrogenation of 19 led to the generation and intramolecular collapse of dienone 20 furnishing 21 and thence 22 with the required structural framework of the target molecules. Finally, esterification with mixed anhydride 24 followed by deprotection gave eleutherobin (1) which served as a precursor to eleuthosides A (2) and B (3). The α-glycoside anomer of eleutherobin, compound 27, was also synthesized by application of the developed chemistry, demonstrating the flexibility of the sequence in generating designed analogues for biological screening.

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COMMUNICATIONS component 7 to give 24, and with subsequent cycloreversion to the conjugated diene 8. The fact that coupling is limited to terminal alkynes may have a steric origin. Formation of the more stable and thus less reactive conjugated carbene complex 23 might explain why the yne-ene metathesis requires longer reaction times than conventional cross-metathesis between alkenes. Volatile ethylene is formed in the cross-metathesis of terminal alkenes, whereas the yne-ene metathesis takes place with atom economy. The driving force in yne-ene metathesis may be the formation of a conjugated diene.The type of reaction described here is, to our knowledge, the first selective crossed yne-ene metathesis. Application of this cross-metathesis between terminal alkynes and alkenes has been demonstrated by the synthesis of variously functionalized dienes. The reaction opens the way to interesting structural elements: thus, conjugated allylsilanes have found a variety of applications, for example in Sakurai reactions.['*] The metathesis products are also of interest with respect to Diels-Alder reactions and cycloadditions. We are currently investigating the applications of yne-ene metathesis in natural product synthesis.

C-Glycosidation is of great significance in the organic synthesis of optically active materials, since it allows the introduction of carbon chains to sugar chirons and the use of sugar nuclei as a chiral pool as well as a carbon source. Silylacetylenes are sufficiently reactive to form 'sugar acetylenes' for the selective introduction of various acetylenic groups in an alpha-axial manner at the anomeric position of D-hexopyranose rings. 1,4-Anti induction, on the other hand, gives a different stereochemical outcome in the case of C-glycosidation of pentopyranose glycals. The mechanism of these reactions includes oxonium cation intermediates in which stereoelectronic and/or steric factors drive the direction of the incoming silylacetylene. Bis-C-glycosidation allows the introduction of sugars at both ends of some bis(trimethylsilyl)acetylenes. A 2,3-dideoxyglucose derivative provides the corresponding C-1 a-acetylenic compounds, which would increase the scope of Cglycosidation with silylacetylenes. In sugar acetylenes, the alkynyl group at the anomeric position of a pyranose ring is epimerized via a hexacarbonyldicobalt complex by treatment with trifluoromethanesulfonic acid. The three steps-cobalt complexation, acidic transformation and decomplexationafford overall epimerization and thus one can obtain either the aor b-alkynyl C-glycoside as desired. Ring opening of a dihydropyran derivative using Nicholas-type cation intermediates is also part of this study. Several sets of decomplexation conditions for endo-type acetylene-cobalt complexes pro-vide various olefins possessing potential utility for synthesis. These methodologies have been utilized for the synthesis of polyoxygenated natural products and derivatives.