Tethered Biginelli Condensation Research Articles

ChemInform Abstract: Preparation of an ABC Tricyclic Model of the Cylindrospermopsin Alkaloids via a Biomimetically Inspired Pathway.

AbstractTricyclic guanidine model compounds (VI) are prepared in 12 steps from pentanediol (I) using a tethered Biginelli condensation between deprotected (II) and β‐keto esters (III) as the key step.

Preparation of an ABC tricyclic model of the cylindrospermopsin alkaloids via a biomimetically inspired pathway

The protected guanidine18was convertedviaa 4-step sequence (Boc-deprotection, tethered Biginelli condensation, deallylation/decarboxylation and reduction) to give the tricyclic guanidines26and27, models of the tricyclic core of cylindrospermopsin1.

ChemInform Abstract: A Biomimetic Approach to the Cylindrospermopsin Alkaloids.

AbstractA tethered Biginelli condensation of hemiaminal derived from compound (I) with β‐keto ester (II) provides access to the tricyclic guanidine moiety found in cylindrospermin alkaloids.

A biomimetic approach to the cylindrospermopsin alkaloids

The tethered Biginelli condensation between hemiaminal 21 and β-keto ester 22 is reported, leading to a model tricyclic core of the cylindrospermopsin alkaloids.

Enantioselective Total Synthesis of Batzelladine F and Definition of Its Structure

Batzelladine F (1) was synthesized in enantioselective and stereoselective fashion in 15 steps (longest linear sequence) and 1.7% overall yield from two readily available enantioenriched beta-hydroxy esters, methyl (R)-3-hydroxydecanoate and methyl (R)-3-hydroxybutyrate. Tethered Biginelli condensations are used to assemble both tricyclic guanidine fragments, with the second tethered Biginelli condensation (14 + 16 --> 17) also being employed to join the guanidine fragments. Three diastereomers of batzelladine F, 2-4, were prepared also. A combination of HPLC, optical rotation and CD spectroscopy was employed to distinguish stereoisomers 1-4, proving that 1 is the correct structure of the hexacyclic marine alkaloid batzelladine F.

The Tethered Biginelli Condensation in Natural Product Synthesis

AbstractFor Abstract see ChemInform Abstract in Full Text.

The tethered Biginelli condensation in natural product synthesis.

This review describes the development of the tethered Biginelli condensation and its application to the total synthesis of structurally complex, bioactive guanidine alkaloids.

Enantioselective Total Syntheses of 13,14,15-Isocrambescidin 800 and 13,14,15-Isocrambescidin 657

The first total syntheses of 13,14,15-isocrambescidin 800 (1) and 13,14,15-isocrambescidin 657 (2) were accomplished in convergent fashion. The central strategic step was tethered Biginelli condensation of guanidine aminal 14 and β-ketoester 15 to give 1-iminohexahydropyrrolo[1,2-c]pyrimidine carboxylic ester 16. This step united all the heavy atoms of the pentacyclic guanidine nucleus and set the critical trans C10−C13 stereorelationship. Acidic treatment of derivative 18 triggered tricyclization to generate pentacyclic guanidine 19b in high yield. After cleavage of the allyl ester, the derived acid underwent coordinated epimerization at C14 and C15 in the presence of triethylamine to form the pentacyclic isocrambescidin nucleus. The synthesis of 1 was achieved in 11% overall yield from amine 12 by a sequence involving five isolated intermediates. As detailed in the preceding account, 12 can be accessed from commercially available 3-butyn-1-ol in 30% overall yield by way of nine isolated and purified int...

A Practical Entry to the Crambescidin Family of Guanidine Alkaloids. Enantioselective Total Syntheses of Ptilomycalin A, Crambescidin 657 and Its Methyl Ester (Neofolitispates 2), and Crambescidin 800

Among the most structurally remarkable guanidine natural products are the crambescidin/ptilomycalin A family of marine alkaloids. The evolution of a practical strategy for preparing pharmacologically significant crambescidin/ptilomycalin A alkaloids that lack oxidation at C13 is described. The first total syntheses of crambescidin 800 (2), crambescidin 657 (6), and neofolitispate 2 (7) are reported in full detail. The central strategic step in these convergent total syntheses is tethered Biginelli condensation of β-keto ester 24 with ureido aminal 61 to combine all carbons of the guanidine nucleus and set the pivotal C10−C13 stereorelationship. The total synthesis of crambescidin 800 (2) was accomplished in 3% overall yield from commercially available 3-butyn-1-ol by way of 16 isolated and purified intermediates. Full details of our earlier total synthesis of ptilomycalin A (1) are also presented. The total syntheses described in this disclosure confirm the stereochemical assignments of 1, 2, 6, and 7 and rigorously establish that the absolute configuration of the hydroxyspermidine side chain of crambescidin 800 (2) is S.

Asymmetric total synthesis of batzelladine D.

[formula: see text] The first enantioselective total synthesis of a batzelladine alkaloid is described. The central reaction in the synthesis of (-)-batzelladine D (2) is a tethered Biginelli condensation of a guanidine aldehyde and an acetoacetic ester to generate a 7-substituted-1-iminohexahydropyrrolo-[1,2-c]pyrimidine intermediate having the anti stereochemistry of the methine hydrogens flanking the pyrrolidine nitrogen.

Application of the Tethered Biginelli Reaction for Enantioselective Synthesis of Batzelladine Alkaloids. Absolute Configuration of the Tricyclic Guanidine Portion of Batzelladine B.

Tethered Biginelli condensation of enantioenriched hexahydropyrrolopyrimidines 8 with beta-ketoesters provides efficient asymmetric access to tricyclic guanidines 9 having a syn relationship of the angular C2a and C8a hydrogens. This reaction was employed to realize the first practical enantioselective access to this fragment of batzelladine alkaloids B (2) and E (5). The efficiency of this strategy is illustrated in the synthesis of the dextrorotatory enantiomer of batzelladine B methanolysis product 10 in 10 steps and 25% overall yield from 2-nonanone and methyl acetoacetate. The asymmetric synthesis of 10 establishes that the absolute configuration of the tricyclic portion of batzelladine B (2) is 25aR,28S,30R. The 4-methyl-7-alkyl-1,2,2a,3,4,5,6,7,8,8a-decahydro-5,6,8b-triazaacenaphthalene-3-carboxylic acid subunit, e.g., 29, of batzelladine alkaloids A (1), D (4), F (6), and G was also prepared for the first time by catalytic hydrogenation of tricyclic guanidines 26 having the 2a,8a-anti stereochemistry.

Studies directed toward anti-HIV compounds

Abstract

ChemInform Abstract: Studies Toward the Total Synthesis of (+)‐Ptilomycalin A. Use of a Tethered Biginelli Condensation for the Preparation of an Advanced Tricyclic Intermediate.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Studies toward the total synthesis of (+)-ptilomycalin A. Use of a tethered Biginelli condensation for the preparation of an advanced tricyclic intermediate

An intramolecular ureidoaldehyde condensation, β-keto ester (16) + 1-carbamoylpyrrolidine ((R)-14) → Pyrrolo[1,2-c]pyrimidine derivative (19), is the key step in a seven-step preparation of the enantiopure spiro[pyrano-2:3-pyrrolo[1,2-c]pyrimidine] derivative (23), a potential intermediate for the enantioselective total synthesis of ptilomycin A