An efficient synthesis of (−)-3-deazaaristeromycin

The coupling reaction of 4-chloro-1H-imidazo[4,5-c]pyridine (6-chloro-3-deazapurine) and (3aS,4S,6R,6aR)-tetrahydro-2,2-dimethyl-6-vinyl-3aH-cyclopenta-[d][1,3]dioxo-4-ol under Mitsunobu reaction conditions provides, after three subsequent straightforward reactions, ready access to the highly biologically active (−)-3-deazaaristeromycin. The versatility of this procedure opens access to a diverse pool of 3-deazapurine carbocyclic nucleosides.     

An efficient synthesis of (R)-3-hydroxytetradecanoic acid

A short, efficient synthesis of (R)-3-hydroxytetradecanoic acid, a key component of bacterial endotoxins, using (R)-oxirane acetic acid ethyl ester as the source of chirality is described. The method is general and can be used in the preparation of other chiral 3-hydroxy acids.     

A facile synthesis of naturally occurring 5-(3-indolyl)oxazoles

A simple and efficient synthesis of naturally occurring 5-(3-indolyl)oxazoles is described. The key steps of this convergent approach are the formation of a 3-tosyloxyacetyl-1-benzenesulfonylindole, a 3-amino-acetyl-1-benzenesulfonylindole hydrochloride and cyclodehydration of an α-acylaminoketone.     

A strategy for the solution-phase parallel synthesis of N-(pyrrolidinylmethyl)hydroxamic acids

Both five- and six-membered iminocyclitols have proven to be useful transition-state analogue inhibitors of glycosidases. They also mimic the transition-state sugar moiety of the nucleoside phosphate sugar in glycosyltransferase-catalyzed reactions. Described here is the development of a general strategy toward the parallel synthesis of a five-membered iminocyclitol linked to a hydroxamic acid group designed to mimic the transition state of GDP-fucose complexed with Mn(II) in fucosyltransferase reactions. The iminocyclitol 8 containing a protected hydroxylamine unit was prepared from D-mannitol. The hydroxamic acid moiety was introduced via the reaction of 8 with various acid chlorides. The strategy is generally applicable to the construction of libraries for identification of glycosyltransferase inhibitors.     

An efficient synthesis of sterically hindered arylboronic acids

Boronic acids are important intermediates and molecular recognition moieties in a wide variety of applications. In our research, we have found that the synthesis of ortho-substituted arylboronic acids is problematic with the commonly used bis(pinacolato)diboron in palladium-mediated borylation reactions. As a substitute, we have found that bis(neopentyl glycolato)diboron is a much more efficient borylation agent for the synthesis of sterically hindered ortho-substituted arylboronic acids.     

Synthesis and transformation of (N-substituted 2-methyl-5-methoxy-3-indolyl)succinic acids

The reaction of N-substituted 2-methyl-5-methoxyindoles with maleic anhydride gave the corresponding (2-methyl-5-methoxy-3-indolyl)succinic anhydrides, which were hydrolyzed to acids and converted to monoamides by reaction with primary or secondary amines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1525–1527, November, 1972.     

An efficient synthesis of (±)-pinidine

A total synthesis of (±)-pinidine I was accomplished starting from the readily available propargylic tosylate 1 and 5-bromo-2-pentanone 2.     

Facile and efficient synthesis of a new class of bis(3′-indolyl)pyridine derivatives via one-pot multicomponent reactions

A series of 4-aryl-3,5-dicyano-2,6-di(3′-indolyl)pyridine derivatives were synthesized via a one-pot multicomponent reaction of aromatic aldehydes, 3-cyanoacetyl indoles, and ammonium acetate under microwave irradiation. Particularly valuable features of this method include high yields of products, broad substrate scope, short reaction time, and straightforward procedure.     

Blue-luminescent 5-(3-indolyl)oxazoles via microwave-assisted three-component coupling-cycloisomerization-Fischer indole synthesis

Aryl-substituted 5-(3-indolyl)oxazoles are readily synthesized in a novel one-pot three-component synthesis consisting of a microwave assisted sequence of Sonogashira coupling, an acid-catalyzed cycloisomerization, and a concluding Fischer indole synthesis. All title compounds are intensely blue-luminescent with large Stokes shifts upon UV-irradiation. The experimental absorption spectra are rationalized by ZINDO-CI computations based upon DFT geometry optimization.     

An efficient synthesis of (E)-(2-arylpyrazino[1,2-a]pyrimidine-4-ylidene)acetonitriles and cyanomethyl appended pyrimidines

A series of (E)-(2-arylpyrazino[1,2-a]pyrimidine-4-ylidene)acetonitriles 5a-j and aryl/heteroaryl tethered pyrimidin-4-yl acetonitriles 6a-e has been synthesized in excellent yields through base catalyzed ring transformation of suitably functionalized 2H-pyran-2-ones 3 using 2-aminopyrazine 4a and arylamidinium salts 4b, separately.     

A general strategy for the synthesis of cyclic N-aryl hydroxamic acids via partial nitro group reduction

We describe a generalized approach to stereocontrolled synthesis of substituted cyclic hydroxamic acids (3-amino-1-hydroxy-3,4-dihydroquinolinones) by selective reduction of substituted 2-nitrophenylalanine substrates. Compounds in this series have antibacterial properties and have also recently been reported as KAT II inhibitors. The key nitrophenyl alanine intermediates are prepared enantioselectively in excellent yield by phase transfer catalyzed alkylation of the corresponding nitrobenzyl bromides. The scope and limitations of the reductive cyclization transformation have been explored with attention to the effects of substitution pattern and electronics on reaction efficiency and byproduct formation. In addition, a novel activated trifluoroethyl ester cyclization strategy has been developed as an alternate approach to the most sterically demanding systems in this series.     

An efficient synthesis of cholanic acids from 20-ketopregnanes

An efficient synthesis of 3β-hydroxy-5-cholanic acid (8) and 3β-hydroxy-Δ⁵-cholanic acid (16) was carried out starting from 5-dihydropregnenolene (1) and pregnenolone (9). The monoacetates (3 and 11), prepared by Grignard reaction of 1 and 9 with 3,3-ethylenedioxypropylmagnesium bromide followed by acetylation, were dehydrated selectively to give the Δ²⁰⁽²²⁾-compounds (4 and 12) which on hydrogenation followed by acid treatment and Jones oxidation yielded 8 and 16, respectively.     

An efficient synthesis of N-methyl amino acids by way of intermediate 5-oxazolidinones

N-Methyl amino acids occur in many natural products. Experimental strategies are presented for a unified approach to the synthesis of N-methyl derivatives through 5-oxazolidinones of the 20 common l-amino acids. The amino acids with reactive side chains that required protecting groups or devoted syntheses for side chain construction for N-methylation to proceed included serine, threonine, tyrosine, cysteine, methionine, tryptophan, asparagine, histidine, and arginine. The studies have provided improved methods for the preparation of N-methyl serine, threonine, and tyrosine. All 20 of the common l-amino acids are now available in suitable forms for solid or solution-phase peptide synthesis.     

Synthesis of new di-(3-indolyl)arenes

1,4-Di-(3-indolyl)benzene 6 and 2,8-di-(3-indolyl)dibenzofuran 12 were synthesized from 1,4-diacetylbenzene and 2,8-diacetyldibenzofuran, respectively, via indole synthetic strategies. Investigation into the acid-catalysed formation of macrocyclic systems from these di-(3-indolyl)arenes led to the development of the 18-membered macrocycle 14 from the diindolylbenzene 6, which was capable of undergoing complexation with nickel(II) ions.     

An efficient two-step synthesis of 3-allylindoles

A two-step synthetic sequence for an efficient synthesis of 3-allylindoles is described.     

Improved preparation of alkyl 2-(3-indolyl)-3-nitroalkanoates under fully heterogeneous conditions: stereoselective synthesis of alkyl (E)-2-(3-indolyl)-2-alkenoates

Ethyl 3-nitro-2-alkenoates can be generated starting from nitroalkanes and ethyl 2-oxoacetate under heterogeneous conditions that minimize work-up procedures, avoid any purification step and direct manipulation of the nitroalkene system. Reaction of ethyl 3-nitro-2-alkenoates, formed in situ from their acetoxy precursors, with indoles in the presence of basic alumina affords ethyl 2-(3-indolyl)-3-nitroalkanoates that are central intermediates for the preparation of tryptamines and carboline alkaloids. A base promoted elimination of nitrous acid from these nitroindolyl derivatives readily produces ethyl 2-(3-indolyl)-2-alkenoates with high E stereoselectivity. The latter compounds can be used as Michael acceptors in intra- and intermolecular reactions with nucleophilic reagents.     

An efficient route for the synthesis of glycosyl phosphinic acids

An efficient method for the synthesis of glycosyl phosphinic acids (21) from the corresponding C-phosphonates is described. The route developed involves three steps: reduction of the glycosyl C-phosphonate to a primary phosphine, reaction of this product with an alkylating agent to afford a secondary phosphine, and finally oxidation to the phosphinic acid. Deprotection provides compounds suitable for testing as glycosyl phosphate analogues. Although the focus of this report is the synthesis of analogues of arabinofuranosyl-containing phosphate esters, the method should be readily applicable to other systems, carbohydrate or otherwise.