Adrián Covarrubias-Zúñiga

A total synthesis of mycophenolic acid

Abstract A total convergent synthesis of mycophenolic acid 1 from 2-geranyl-dimethyl-1,3-acetonedicarboxylate 2 and 4-pivaloyloxy-2-butynal using a Michael addition-Dieckmann cyclization as key step is described.

Total synthesis of mycophenolic acid

Abstract A convergent total synthesis of the natural compound mycophenolic acid 1 is described. The synthetic strategy for the construction of the hexasubstituted aromatic nucleus was based on a ring annulation sequence, involving a Michael addition reaction and intramolecular Dieckmann condensation reaction in situ as the key step. Subsequent transformations of the substituents afforded the target mycophenolic acid 1 .

A SIMPLE PREPARATION OF N,N-DIMETHYL-N′-ALKYL (ARYL) SULFONYLFORMAMIDINES

1. (a) M. G. Saulnier and G. W. Gribble, Tetrahedron Lett., 24,5435 (1983). (b) G. W. Gribble, M. G. Saulnier, M. P. Sibi and J. A. Obaza-Nutaitis, J. Org. Chem., 49,4518 (1984). (c) G. W. Gribble and M. G. Saulnier, J. Chem. SOC., Chem. Commun., 168 (1984). (d) D. A. Davis and G. W. Gribble, Tetrahedron Left., 31, 1081 (1990). (e) G. W. Gribble, D. J. Keavy, D. A. Davis, M. G. Saulnier, B. Pelcman, T. C. Barden, M. P. Sibi, E. R. Olson and J. J. BelBruno, 1. Org. Chm. , 57,5878 (1992). (f) G. W. Gribble, R. A. Silva and M. G. Saulnier, Synrh. Commun., 29,729 (1999).

SYNTHESIS OF RESORCINOLS VIA A MICHAEL ADDITION-DIECKMAN CYCLIZATION SEQUENCE OF DIMETHYL 1,3-ACETONEDICARBOXYLATE ANION WITH ALKYL ALKYNOATES

The reaction of dimethyl 1,3-acetonedicarboxylate anion 1 with a number of alkyl alkynoates gives unsymmetrical (from alkynoates 2a-g) or symmetrical (from alkynoates 2h-i) resorcinols, in a one po...

One Pot Synthesis of Phenolic Compounds from Aliphatic Ones.

Abstract Synthesis of tetra and pentasubstituted phenols from dimethyl 1,3-acetonedicarboxilate anion 1 and alkinones 2 is described. The salient feature of this procedure is to provide phenols with regiocontrol at the 3/5 positions. This research was supported by a Grant-in-Aid for Scientific Research No. 40361-53352E from CONACYT, Mexico. Contribution No. 0000 of Instituto de Quimica, UNAM.

A Convenient Procedure for the Synthesis of 4,6-Disubstituted 2-OXO-2H-Pyran-5-carboxylic Esters.

Abstract A simple procedure for the synthesis of 2H-pyran-2-ones 2a is described: The initial Michael addition product of β-ketoester anions with acetylenic esters readily cyclizes under the basic reaction conditions to give the α-pyrones 2a (Scheme 2).

A Short Synthesis of (±)‐Sporochnol A, A Chemical Fish Deterrent from a Caribbean Marine Alga

Abstract A short formal synthesis of (±)‐sporochnol A (1) is described. In this synthesis, the quaternary carbon center is formed by successive alkylations of the carbanion α to the nitrile in an arylacetonitrile derivative, followed by conversion of the nitrile group to a vinyl group. The quaternary carbon center derivatives obtained in each step were characterized by spectroscopy.

Alkylation of Dimethyl 1,3-Acetonedicarboxylate

Abstract A reliable, reproducible, general, and detailed procedure for the alkylation of dimethyl-1,3-acetonedicarboxylate is described.

A Total Synthesis of the Antibiotic DB-2073

Abstract A convergent aromatic annulation strategy based on the Michael addition of the dimethyl-1,3-acetonedicarboxylate 1 anion to 2-hexynal 2, followed by a regiocontrolled Dieckmann-type cyclization, has been applied to a total synthesis of the antibiotic, DB-2073 I. This tandem annulation reaction generates the fully substituted aromatic intermediate 3, which was transformed by a five-step sequence to I. In recent years we have developed a total and a formal synthesis of mycophenolic acid [Covarrubias-Zúñiga, A.; González-Lucas, A. Tetrahedron Lett. 1998, 39, 2881; Covarrubias-Zúñiga, A.; Díaz-Domínguez, J.; Olguín-Uribe, J.S. Synthetic Communications 2001, 31, 1373.] using as key step tandem reactions based on Michael addition and intramolecular Dieckmann-cyclization; In this article we utilize this synthetic approach for the total synthesis of the resorcinol DB-2073 I. This tetrasubstituted resorcinol was isolated and purified from pseudomonas B-9004, showing antibacterial and antifungal activities [Kanda, N.; Ishizaki, N.I.; Oshima, M.; Handa, A.; Kitahara, T.J. Antibiotics 1975, 28, 935.]. The molecular formula of DB-2073 was established by spectroscopic methods [Kitahara, T.; Kanda, N. J. Antibiotics 1975, 28, 943.], as 2-hexyl-5-propyl-resorcinol I.

SIMPLE AND PRACTICAL SYNTHESES OF DIBENZYL, BENZYL ETHYL AND BENZYL METHYL MALONATES

The classical malonic ester synthesis is a widely used method to prepare homologous carboxylic acids andor esters from alkyl halides, but in some cases has the disadvantage of the strongly basic conditions required for the conversion of alkylated malonate to monocarboxylic acid. It is known that benzyl esters can release the corresponding carboxylic acids by hydrogenol ysis under essentially neutral conditions. Hence, a simple modification to circumvent this problem is the use of benzyl malonates such as 1-3 which are however, very expensive chemicals.