Víctor S. Martín

Stereo and regioselective openings of chiral 2,3-epoxy alcohols. Versatile routes to optically pure natural products and drugs. Unusual kinetic resolutions

A diverse selection of new synthetic applications of the titaniumcatalyzed asymmetric epoxidation (AE) process is described. These include asymmetric syntheses of (+)_DarvonR Alcohol, (-)-bestatin, (+)-2-methyl bestatin, (-)-propranolol, (-)-u-amino--hydroxybutyric acid, and (_) and (+)_frontalin. The kinetic resolution mode of the AE process was used to prepare chiral insect pheromones in very high (>99% e.e.) optical purity; these include (+)-and (-)-ct-caprolactone, (-)-exobrevicomin, (-)-endobrevicomin, (+)_and (-)-ipsdienol, and (+)-trans-verbenol. A number of unusual kinetic resolutions based on the AE process are presented; these include resolutions of allenic alcohols, n-acetylenic carbinols, -hydroxy sulfides, and a dienol. Almost two years ago we first reported on the titanium-catalyzed asymmetric epoxidation process shown in Scheme 11a In the interim this new chiral catalyst system has rapidly become accepted as one of the best means for synthesizing a great variety of optically pure

A new catalytic Prins cyclization leading to oxa- and azacycles.

A new Prins cyclization process that builds up one carbon-carbon bond, one heteroatom-carbon bond, and one halogen-carbon bond, (in an oxa- and azacycle) relies on an iron catalyst system formed from Fe(acac)3 and trimethylsilyl halide. The method displays a broad substrate scope and is economical, environmentally friendly, and experimentally simple. This catalytic method permits the construction of chloro, bromo and iodo heterocycles, by the suitable combination of iron(III) source, the corresponding trimethylsilyl halide and the solvent, in high yields.

Enantiospecific synthesis of α-amino acid semialdehydes: a key step for the synthesis of unnatural unsaturated and saturated α-amino acids

Abstract The enantiospecific synthesis of unnatural unsaturated and saturated α-amino acids based on a Wittig type reaction is described. The versatile synthetic intermediates, l -glutamic and l -aspartic acid semialdehydes, are obtained from the corresponding N , N -di-Boc-diesters, by the selective reduction of the ω-ester with DIBAL ® under controlled conditions. The semialdehydes are chemically stable for a prolonged time and react with various phosphorous ylides, under controlled conditions, to produce the enantiomerically pure unsaturated α-amino acids in high yields. The method is equally applicable to homologated diesters obtained by the presented methodology providing unsaturated amino acids with variable unsaturated positions and geometries. The corresponding saturated products can be obtained by simple hydrogenation.

Prins-Type Synthesis and SAR Study of Cytotoxic Alkyl Chloro Dihydropyrans

A series of functionalized tetrahydropyran and dihydropyran derivatives was synthesized by means of a Prins‐type cyclization between unsaturated alcohols and several aldehydes. An unprecedented dimer bearing two 4‐chloro‐5,6‐dihydro‐2H‐pyran scaffolds was obtained in high yield. A panel of three representative human solid tumor cells from diverse origin was used to assess the cytotoxicity of the compounds. Overall, the results show the relevance of the chlorovinyl group in the biological activity, and 2‐alkyl‐4‐chloro‐5,6‐dihydro‐2H‐pyrans represent interesting leads for further chemical modifications and biological studies.

Non-terpenoid C-15 metabolites from the red seaweed Laurencia pinnatifida☆

Abstract The structures of absolute configurations of the halogenated vinyl acetylenes which are natural products from the red alga Laurencia pinnatifica (Gmal. Lamour) are described. The structure of trans - pinnatifidenyne 2 was determined by spectral, chemical and X-ray diffraction analyses. The structure of cis -pinnatifidenyne 1 is based on spectral comparison and chemical interconversion with the trans -isomer 2 . The structure of the acyclic trienyne 8 was secured as: (6 R ,7 R )-3- cis , 9- cis ,12- cis ,6-acetoxy,7-chloropentadeca-3,9,12-trien-1-yne by synthesis from cis -pinnatifidenyne 1 . The reactivity of these compounds to various conditions of catalytic hydrogenation has been examined in detail.

A stereoselective synthesis of medium-sized cyclic ethers by the intramolecular cyclization of linear hydroxyalkyl-propargylic alcohols assisted by Co2(CO)8

A highly efficient, mild and general cyclization reaction of hydroxy exo-(propargyl)Co2(CO)6 cations leading to medium-sized (6 to 9 membered) cyclic ethers is described. The reaction is highly stereoselective when defined stereocenters are encountered in the linear precursor, providing a way to obtain fused cyclic ethers in their enantiomeric forms.

Stereocontrolled synthesis of cyclic ethers by intramolecular hetero-Michael addition. 4. Enantiomeric synthesis of substituted and fused oxepanes

The use of an intramolecular hetero-Michael addition of enantiomerically enriched 7-alkoxy-4-benzoyloxy-2,3-unsaturated esters for the synthesis of endo-substituted oxepanes is described. The stereochemistry in the cyclization step is governed by the geometry of the double bond in the unsaturated ester and the presence of a Z-double bond in the linear chain is required in order to achieve good yields. The synthesis of the fused oxepane-tetrahydropyran nucleus of marine polyether toxins with absolute control of all the stereocentres is described.

Biomimetic approach to the synthesis of rhodolaureol and rhodolauradiol

Abstract It is postulated that 9-hydroxy-β-iso-obtusene ( 4 ) is the biogenetic precursor of the tricyclic sesquiterpenoids rhodolauradiol ( 7 ) and rhodolaureol ( 9 ). The transformation 4 → 7 was carried out under non-enzymic conditions.

Insect growth regulatory effects of linear diterpenoids and derivatives from Baccharis thymifolia.

Linear diterpenes isolated from aerial parts of Baccharis thymifolia ( 1- 3) were tested for insect growth inhibitory activity against Tenebrio molitor larvae. Compounds 4- 16 were prepared by various chemical transformations. The diterpenes 6,10-( E,E)-thymifodioic acid ( 1), the butenolide 3, and the derivatives 4, 11, and 14 produced developmental deficiencies in assays using topical application on fifth instar larvae of T. molitor. Compound 3 is a new natural product.

An Approach to Lauroxanes by Iterative Use of Co2(CO)6-Acetylenic Complexes. A Formal Synthesis of (+)-Laurencin

A new approach to lauroxanes by a powerful and highly convergent methodology based on iterative use of Co(2)(CO)(6)-acetylenic complexes is described. The strategy employs an intermolecular Nicholas reaction to form unsaturated branched linear ethers, a ring closing metathesis to obtain the cobalt complex cyclic ethers, and an isomerization promoted by montmorillonite K-10. A short synthesis of cyclic ethers of seven-, eight-, and nine-membered rings is described. Additionally, the methodology is exemplified by the formal synthesis of (+)-laurencin, a red algae metabolite.