Stereoselective synthesis of 3,3-diarylacrylonitriles as tubulin polymerization inhibitors

A series of 3,3-diarylacrylonitriles were synthesized stereoselectively as tubulin polymerization inhibitors for potential use in cancer chemotherapy. This synthetic route features stannylcupration and palladium-catalyzed Stille cross-coupling chemistry, allowing both E and Z isomers of 3,3-diarylacrylonitriles to be prepared in a very short sequence of reactions.     

Stereoselective total synthesis of preclavulone-A methyl ester and its diastereomer

The total synthesis of preclavulone-A methyl ester and its diastereomer was achieved from same key intermediate in diastereoselective manner. These compounds are recognized as important intermediates in a proposed biosynthesis of marine prostanoids from the Okinawan soft coral, Clavularia viridis, and were recently isolated from the extract of C. viridis by our group.     

Stereoselective synthesis of methyl monate C

[Structure: see text] The stereoselective synthesis of methyl monate C 2 is described using as a key step an ene-intramolecular modified Sakurai cyclization (IMSC) reaction to prepare tetrahydropyran 5. An asymmetric allylic alkylation, followed by a cross-metathesis, enables the insertion of the right-hand side chain.     

Stereoselective synthesis of methyl 7-dihydro-trioxacarcinoside B

A stereoselective synthesis of 7-dihydro-triocacarcinose B, a branched octose from the quinocyclines, has been achieved. The biocatalytic resolution of a Baylis-Hillman adduct and a subsequent ring-closing metathesis were used to assemble the molecular framework. Subsequent key steps were a highly stereoselective epoxidation and a regio- and stereoselective opening of the epoxide by allyl alcohol and HClO4 to introduce the C(3)-OH group in protected form. The 7-dihydro-triocacarcinose B could be converted into the corresponding 1,7-anhydrosugar.     

Total synthesis of zincophorin methyl ester

[reaction: see text]. A convergent total synthesis of the methyl ester of zincophorin, an ionophore antibiotic, has been realized relying on a diastereoselective titanium-mediated aldol coupling between the C1-C12 and C13-C25 subunits. The latter fragment was prepared by using a Carroll-Claisen rearrangement.     

Stereoselective synthesis of photoreactive peptidomimetic gamma-secretase inhibitors

The first asymmetric synthesis of novel, potent photoreactive gamma-secretase inhibitors 2 and 3 has been accomplished. Two stereoselective methods for the preparation of lactone 9 are described. Protected benzophenone intermediate 19 is prepared via an aldol-elimination reaction followed by a PtO(2)-catalyzed asymmetric hydrogenation. Two routes leading from 19 to compounds 2 and 3 are evaluated. The application of 3 as an activity-based probe has been demonstrated by localizing gamma-secretase activity in the plasma membrane of intact cells.     

Total synthesis of zincophorin and its methyl ester

A total synthesis of the naturally occurring ionophore zincophorin has been realized. The route features an intramolecular oxymercuration of a cyclopropanemethanol and a Carroll-Claisen rearrangement for the respective elaboration of the C1-C12 and C13-C25 subunits, which have been assembled by using a highly diastereoselective titanium-mediated aldol condensation.     

Convergent synthesis of leukotriene a methyl ester

A convergent total synthesis of methyl 5,6-oxido-7,9,11,14-eicosapentaenoate from oct-2-yn-l-ol and metyl 4-formylbutyrate is described.     

Total synthesis of stephanotic acid methyl ester

[structure: see text]The methyl ester of the naturally occurring macrocyclic pentapeptide stephanotic acid, containing an unusual beta-substituted alpha-amino acid with a tryptophan C-6 to leucine beta-carbon link, has been synthesized. The key steps include the formation of this amino acid through a thioxo-oxazolidine intermediate and a Horner-Wadsworth-Emmons reaction using a phosphonoglycine, derived by a dirhodium(II)-catalyzed N-H insertion reaction, to give a dehydroamino acid and subsequent rhodium(I)-catalyzed asymmetric hydrogenation to introduce the modified tryptophan residue.     

Photo-copolymerization of methacryloyl-L-valine methyl ester,methacryloyl-D-valine methyl ester,and maleic anhydride

Photocopolymerization of methacryloyl-L -valine methyl ester (L-MAVM), methacryloyl-D -valine methyl ester (D-MAVM) and maleic anhydride (MAn) was carried out in dioxane at 25°C without initiator at an initial total concentration of the three monomers of 1 mole/1.; the molar ratio of MAn in the feed to the sum of L- and D-MAVM was 1 : 1 in all cases. The copolymer with a 1 : 1 molar ratio of MAVM and MAn was always obtained regardless of the feed molar ratio of L- and D-MAVM. The circular dichroism (CD) spectra of the copolymer before and after hydrolysis showed a linear relationship between the monomer unit ellipticity at 222 nm and the molar feed ratio of L- and D-MAVM and suggested the induction of an asymmetric center into the polymer main chain. The results also indicated that the configuration of the induced asymmetric carbon atoms would be arranged according to that of fed MAVM monomer.     

Single-site anionic polymerization. Monomeric ester enolaluminate propagator synthesis, molecular structure, and polymerization mechanism

The synthesis and molecular structure of the first examples of monomeric lithium ester enolaluminates that serve as structural models for single-site anionic propagating centers, as well as the mechanism of their polymerization of methacrylates catalyzed by conjugate organoaluminum Lewis acids, are reported. Reactions of isopropyl alpha-lithioisobutyrate (2) with suitable deaggregating and stabilizing organoaluminum compounds such as MeAl(BHT)2 (BHT = 2,6-di-tert-butyl-4-methylphenolate) in hydrocarbons cleanly generate lithium ester enolaluminate complexes such as Li+[Me2C=C(OiPr)OAlMe(BHT)2]- (3). Remarkably, complex 3 is isolable and exists as a monomer in both solid and solution states. Unlike the uncontrolled polymerization of methacrylates by the aggregating enolate 2, the methacrylate polymerization by the monomeric 3 is controlled but exhibits low activity. However, the well controlled and highly active polymerization can be achieved by using the 3/MeAl(BHT)2 propagator/catalyst pair, which is conveniently generated by in situ mixing of 2 with 2 equiv of MeAl(BHT)2. The structure of the added organoaluminum compounds has marked effects on the degree of monomer activation, enolaluminate formation and reactivity, and polymerization control. Kinetics of the polymerization by the 3/MeAl(BHT)2 pair suggest a bimolecular, activated-monomer anionic polymerization mechanism via single-site ester enolaluminate propagating centers. The molecular structures of activated monomer 1, aggregated initiator 2, and monomeric propagator 3 have been determined by X-ray diffraction studies.     

Enantioselective synthesis of preclavulone A and its methyl ester

A highly enantioselective synthesis of the (8S,12S)-enantiomer of preclavulone A and its methyl ester is described featuring the Julia protocol for installing the (Z)-double bond in the lower chain. This procedure is suitable for the preparation of labeled preclavulone analogues for biosynthetic studies on marine clavulones.     

Stereoselective synthesis of 2-azetidinones as cholesterol-absorption inhibitors

The synthesis of two 2-azetidinones possessing powerful cholesterol-absorption inhibition properties has been accomplished by a short and highly stereoselective reaction sequence. The key step is the condensation of the titanium enolate of the easily prepared 2-pyridylthioester (R)-11 with imine 6 which affords the desired β-lactam intermediate in the correct relative and absolute configuration. Conversion to the pharmacologically active compounds is readily accomplished by simple functional group manipulation.     

The regiospecific total synthesis of lavendamycin methyl ester

The total synthesis of the methyl ester of the antibiotic lavendamycin (4a) by an 8-step sequence from 8-methoxyquinaldic acid (6) is described.     

Shanzhisin methyl ester gentiobioside,a new iridoid - isolation and synthesis

The title compound 1 has been isolated from $\text{Canthium subcordatum}$ and its structure deduced; 1 was synthesised from shanzhiside methyl ester.