Esteban Alvarez

A Very Efficient Route toward the 4a-Methyltetrahydrofluorene Skeleton: Short Synthesis of (±)-Dichroanone and (±)-Taiwaniaquinone H

A very expedient and efficient new route toward taiwaniaquinoids, bearing the 4a-methyltetrahydrofluorene skeleton, is reported. Key steps are the intramolecular Friedel-Crafts alkylation of an aryldiene and the degradative oxidation of a methylenedioxy group; the latter process could also be utilized for building the 2-hydroxy-1,4-benzoquinone unit, which is frequently found in natural products. Utilizing this new methodology, (+/-)-dichroanone (7) (three steps, 77% overall yield) and (+/-)-taiwaniaquinone H (6) (four steps, 70% overall yield) have been synthesized from commercial alpha- (11a) or beta-cyclocitral (11b).

General Access to Taiwaniaquinoids Based on a Hypothetical Abietane C7–C8 Cleavage Biogenetic Pathway

A new strategy for synthesizing taiwaniaquinoids, a group of terpenoids with an unusual rearranged 5(6→7) or 6-nor-5(6→7)abeo-abietane skeleton, which exhibit promising biological activities, is reported. The procedure, based on the cleavage of the C7-C8 double bond of abietane diterpenes, is the only one yet reported for synthesizing C(20) taiwaniaquinoids bearing a carbon function on the cyclopentane B ring; it is also applicable to the synthesis of the wide variety of existing taiwaniaquinoids. Utilizing this, (-)-taiwaniaquinone A, F, G, and H, (-)-taiwaniaquinol B, and (-)-dichroanone have been synthesized from (+)-abietic acid. The versatility of this strategy allows us to propose the abietane C7-C8 cleavage as a possible biosynthetic pathway to this type of rearranged diterpenes; this proposal seems to be supported by phytochemical evidence.

NIS–PPh3: A Selective Reagent for the Spiroannulation of o-Allyl Phenols. Total Synthesis of Corallidictyal D

Treatment of o-allyl phenols with catalytic NIS-PPh3 affords the corresponding spirodihydrobenzofuran derivatives in high yield with high regio- and total stereoselectivity under mild conditions. These results were utilized to achieve the first total synthesis of the protein kinase C inhibitor corallidictyal D starting from α-ionone.

Stereoselective transformations of (+)-abietic acid into (+)-vitedoin B and (+)-negundoin A.

The first synthesis of spirolactone (+)-vitedoin B (14 steps, 8.0% global yield) and spiro enol ether (+)-negundoin A (19 steps, 3.7% global yield), via a nor-labdane acetoxy ester, has been achieved starting from commercial (+)-abietic acid.

First synthesis of antitumoral dasyscyphin B.

The first synthesis of dasyscyphin B, an antitumoral metabolite obtained from the ascomycete Dasyscyphus niveus, has been achieved starting from commercial abietic acid. The key steps of the synthetic sequence are the diastereoselective α-methylation of a ketoaldehyde, followed by an intramolecular aldol condensation and the further Diels-Alder cycloaddition of a dienol ester. The procedure reported will allow the synthesis of related metabolites functionalized in the A ring.

Synthesis of the putative structure of 15-oxopuupehenoic acid.

Synthesis of the putative structure of the marine natural 15-oxopuupehenoic acid has been achieved starting from commercial (-)-sclareol. Key steps of the synthetic sequence are the Robinson annulation of a β-ketoester and methyl vinyl ketone and an unprecedented cyclization of the resulting α,β-enone, which is mediated by tin(IV) chloride in the presence of N-phenylselenophthalimide. The physical properties of the synthetic compound are somewhat different from those reported for the natural product.

A proportional hazard model with time-dependent parameters and covariates

In this paper we study a fully parametric proportional hazards model in which the covariates as well as the parameters of the base distribution can vary with time. We consider the application of this model to the case of extreme value base-line distribution with rightcensored data and obtain the equations for the estimate by maximum likelihood from the model parameters.