Pilar M. Fresneda

Synthesis of the indole alkaloids meridianins from the tunicate Aplidium meridianum

Abstract The marine natural products meridianins A and C–E have been synthesized for the first time starting from the appropriate N-tosyl-3-acetylindole. A facile two-step conversion of N-tosyl-3-acetylindoles to the corresponding meridianins by treatment with dimethylformamide dimethylacetal and further cyclization of the resulting enaminone with aminoguanidine is described. This method has also been applied for the preparation of the 3-[(2-amino)pyrimidin-4-yl]-7-azaindole.

Synthetic studies towards the 2-aminopyrimidine alkaloids variolins and meridianins from marine origin

A nine-step synthesis of 9-amino-4-methoxypyrido[3 0 ,2 0 :4,5]pyrrolo[1,2-c]pyrimidine, a tricyclic ring system present in the marine alkaloids variolins is described. The natural marine products meridianins C‐E have been synthesized for the first time starting from N-protected 3-acylindoles. # 2000 Elsevier Science Ltd. All rights reserved.

IMINOPHOSPHORANE-MEDIATED SYNTHESES OF THE FASCAPLYSIN ALKALOID OF MARINE ORIGIN AND NITRAMARINE

Abstract New and efficient syntheses of the fascaplysin alkaloid of marine origin and nitramarine are described. In both syntheses the key step, formation of the β-carboline ring, involve a tandem aza-Wttig/electrocyclic ring closure process.

A novel approach to the indoloquinoline alkaloids cryptotackieine and cryptosanguinolentine by application of cyclization of o-vinylsubstituted arylheterocumulenes

Abstract 1-Methyl-3-( o -azidophenyl)quinoline-2-one prepared by cyclization of the corresponding o -vinylsubstituted isocyanate under microwave irradiation is directly converted into cryptotackieine 1 by an intramolecular aza-Wittig reaction with trimethylphosphine; alternatively heating followed by reduction of the resulting indoloquinoline derivative provided cryptosanguinolentine 2 .

A divergent approach to cryptotackieine and cryptosanguinolentine alkaloids

Abstract A seven-step synthesis of the 1-methyl-3-( o -azidophenyl)quinolin-2-one, a common intermediate for the synthesis of the cryptotackieine and cryptosanguinolentine alkaloids, is described. This intermediate is directly converted into cryptotackieine 1 by an intramolecular aza-Wittig reaction with trimethylphosphine; alternatively heating followed by reduction of the resulting indoloquinoline derivative provided cryptosanguinolentine 2 .

A convergent approach to midpacamide and dispacamide pyrrole-imidazole marine alkaloids

Abstract A two-step synthesis of the N -acylated α-azido-ω-aminovalerate, a common intermediate for the synthesis of midpacamide and dispacamide, is described. This intermediate undergoes cyclization through the corresponding α-ureido ester derivative to give the 3-methylhydantoin ring present in midpacamide, whereas the reaction with triphenylphosphine, tosyl isocyanate and ammonia followed by cyclization of the resulting guanidine derivative provides the 2-aminoimidazole ring present in dispacamide.

Iminophosphorane-mediated imidazole ring formation: A new and general entry to aplysinopsin-type alkaloids of marine origin.

Abstract Aza Wittig-type reactions of iminophosphoranes 21, derived from ethyl α-azido-β-(3-indolyl)propenoates and triphenylphosphine, with methyl isocyanate, carbon dioxide or carbon disulfide provide the corresponding heterocumulenes 22, 25 and 28 which undergo cyclization by the action of nitrogenous reagents completing the assemblage of the framework of aplysinopsin. Further deprotection leads to naturally occurring aplysinopsin analogues.

An iminophosphorane-mediated efficient synthesis of the alkaloid eudistomin U of marine origin

Abstract The first synthesis of the alkaloid Leucettamine B, by a four-step sequence in a overall yield of 50%, is discribed. The key step, formation of the 2-aminoimidazole ring, involves a tandem aza-Wittig/carbodiimide-mediated annulation process.

Investigative studies on the formation of the imidazo [4′,5′:3,4]pyrido[2,3-b]indole ring: Formal synthesis of the alkaloids grossularines-1 and 2. X-Ray crystal structures of 5-indol-3-yl-imidazole and bisimidazocarbazole derivatives

Abstract Reactions of several 2,3-disubstituted indoles, bearing a chlorine or amino function at position 2 and an 1,2-dicarbonyl group or bromoacetyl substituent at position 3, with N,N-dimethylguanidine is reported. In general, 5-indol-3-yl imidazole derivatives are found to be the reaction products, however when the 3-bromoacetyl-2-tertbutoxycarbonylaminoindole is used the 2-dimethylamino-4-hydroxy-6-methoxymethyl-3H-imidazo[4′,5′:3,4]pyrido[2,3-b]indole is obtained through a step-wise formation of the pyridine and the imidazole rings. The crystal molecular structure of 5.H2O and 7 . HBr.H 2 O . 3 2 EtOH have been determined by X-Ray analysis. The water molecules in 5. H2O act as both donor (OH…N) and acceptor (NH…O) and are responsible for the formation of strands along the b axis.

A simple and general entry to Aplysinopsine- type alkaloids by tandem Aza-Wittig/heterocumulene-mediated annelation.

Abstract Aza/Wittig-type reactions of iminophosphorane 8 , derived from ethyl α-azido-β-(3-indolyl)propenoate and triphenylphosphine. with methyl isocyanate, carbon dioxide or carbon disulfide lead to the corresponding heterocumulenes 9 , 10 , and 11 which undergo cyclization by the action of nitrogenous reagents to give Aplysinopsine derivatives.