New pyrano[3,4-b]indoles from 2-hydroxymethylindole and l-dehydroascorbic acid

2-Hydroxymethylindole reacts with l-dehydroascorbic acid under mild conditions to give (3R,3aR,10cS)-3-[(1S)-1,2-dihydroxyethyl]-3a,10c-dihydroxy-3a,5,6,10c-tetrahydrofuro[3′,4′:5,6]pyrano[3,4-b]indol-1(3H)-one. Its tosyl derivative undergoes cyclization to form a pentacyclic ketal derivative.     

BH3 as a protecting group for phosphonic acid: a novel method for the synthesis of dinucleoside H-phosphonate

A BH₃ group is found to be an effective protecting group for phosphonic acid esters. This new phosphonic acid protecting group was applied to the synthesis of a dithymidine H-phosphonate derivative from a dithymidine boranophosphate derivative. Triarylmethyl cations were found to be effective for the deprotection of the BH₃ group in the dithymidine boranophosphate diester to afford the corresponding H-phosphonate derivative in excellent yield.     

Synthesis and photochemistry of 3-(o-stilbeneyl)-4-H/Me/Ph-sydnones; intramolecular cyclization to 1,2-benzodiazepines and/or quinolines

Stilbeneylsydnone derivatives were synthesized by a sequence of reactions in good yields. Irradiation of 3-stilbeneyl-4-methylsydnone 4 gives 1H-1,2-benzodiazepine derivative 7 as the main product along with 2-methylquinoline derivative 20. Irradiation of 3-stilbeneyl-4-phenylsydnone 5 afforded only 1H-1,2-benzodiazepine derivative 8 whereas on irradiation of 4-unsubstituted 3-stilbeneylsydnone 3 no benzodiazepine derivative was detected. An efficient novel photochemical approach to 1H-1,2-benzodiazepines has been found from the new 3-(o-stilbeneyl)-4-substituted-sydnones via intramolecular 1,7-electrocyclization reaction of the photogenerated nitrile imines.     

Synthesis and reactions of nitro derivatives of hydrogenated cardanol

3-n-Pentadecylphenol (hydrogenated cardanol) and its derivative 5-n-pentadecyl-2-tert-butylphenol can be nitrated using nitric acid in acetonitrile or methanol to give mono, di or trinitro products. 5-n-Pentadecyl-2-nitrophenol undergoes reductive carbonylation to give a benzoxazole-2-one derivative. An efficient catalytic oxidation reaction in the presence of MeReO₃ has also been studied.     

Facile synthesis of 2′-O-cyanoethyluridine by ring-opening reaction of 2,2′-anhydrouridine with cyanoethyl trimethylsilyl ether in the presence of BF3·Et2O

In this Letter, a facile method for the synthesis of 2′-O-cyanoethyluridine, which is a key intermediate in the synthesis of fully and partially 2′-O-cyanoethylated oligoribonucleotides as well as unmodified oligoribonucleotides, was developed by the ring-opening reaction of 2,2′-anhydrouridine with 2-cyanoethyl trimethylsilyl ether in the presence of BF₃·Et₂O in dimethylacetamide. The 2′-O-cyanoethyluridine 3′-phosphoramidite derivative was converted into the 2′-O-cyanoethyl-4-N-acetylcytidine 3′-phosphoramidite derivative by a series of reactions involving displacement of the 4-(1H-1,2,4-triazol-1-yl)uridine derivative with ammonia followed by acetylation.     

New reactions of 2,3-diaminonaphthaline with carbonyl electrophiles

The reaction of 2,3-diaminonaphthalene with dimedone gave 3-[(3-amino-2-naphthyl)amino]-5,5-dimethylcyclohex-2-en-1-one that reacts with alloxan to afford a product of addition at the enamine moiety. The latter is converted to a spiro derivative on heating in CF₃COOH, or undergoes condensation with 2,6-di-tert-butyl-p-benzoquinone to give a benzophenazinone derivative with a sterically hindered phenol substituent.     

Synthesis of all the six components of the female-produced contact sex pheromone of the German cockroach, Blattella germanica (L.)

All of the following six components of the female sex pheromone of the German cockroach, Blattella germanica (L.) were synthesized: (3S,11S)-3,11-dimethyl-2-nonacosanone (1), its 29-hydroxy derivative 2, its 29-oxo derivative 3, (3S,11S)-3,11-dimethyl-2-heptacosanone (4), its 27-hydroxy derivative 5, and its 27-oxo derivative 6. Both the enantiomers of citronellal were employed as the chiral sources and Wacker oxidation was employed for the introduction of the carbonyl group at C-2.     

Carbon-branched carbohydrate chirons: synthesis of C-3 and C-4-branched sugar lactones derived from d-erythronolactone

Two carbon chain extensions using a Wittig reaction on both a 1-deoxy ribulose derivative and a C-2-branched erythrose derivative are reported. Subsequent dihydroxylation resulted in the synthesis of C-3 and C-4 methyl-branched sugar lactones, the useful synthetic building blocks. Control of the stereoselectivity of both the Wittig reaction and the dihydroxylation is investigated, and 3-C-methyl and 4-C-methyl d-altrono-1,4-lactones and d-glucono-1,4-lactone and 4-C-hydroxymethyl-d-altrono-1,4-lactone were synthesised.     

Studies in the chemistry of erythrina alkaloide derivatives—II : Synthesis and stereochemistry of decahydro-3-methyl-6H-pyrido]2,1-i]indole

1,2,3,4,7,7a,8,9,10,11-Decahydro-3-methyl-6$\text{H}$-pyrido[2,1-i]indole was prepared as an example of an erythrinane derivative lacking the aromatic moiety. The stereochemical structure of this compound and its 6-oxo derivative were found to be predominantly cis A/B, trans B/C, axial CH₃ and cis A/B, axial CH₃, respectively.     

A practical chromatography-free synthesis of a 5,6-dihydroimidazolo[1,5-f]pteridine derivative as a polo-like kinase-1 inhibitor

A practical chromatography-free synthesis of a potent polo-like kinase-1 inhibitor possessing a unique 5,6-dihydroimidazolo[1,5-f]pteridine structure has been developed. We showed that key cyanoimidazole ring formation could be conducted at benign temperature and obtained a chiral 5,6-dihydroimidazolo[1,5-f]pteridine derivative in good yield without epimerization. An aniline derivative containing a trans 1,4-cyclohexyl diamine structure was prepared by a synthesis that makes use of defined stereocenters of commercially available trans-cyclohexane-1,4-diamine via selective piperazine ring formation from a primary diamine. A coupling reaction of the 3-chloro-5,6-dihydroimidazolo[1,5-f]pteridine derivative and the aniline derivative in the endgame was closely investigated, and good yields were achieved both by palladium-catalyzed amination and acid-promoted coupling under benign reaction conditions. As a result of these investigations, the polo-like kinase-1 inhibitor was successfully obtained in a practical way without concern for generation/separation of stereoisomers.     

Porphyrines synthètiques porteuses de chaînes laterales peptidiques-III: Couplage de dipeptides sur l'acide zinc(mésotétraphénylporphyrinyl)-3 propènoique cis ou trans; préparation de derivés pentacoordines

An optimized synthesis of cisendo 3-propenamide-zinc mesotetraphenylprophyrin bearing a C protected dipeptide is described. The choice of zinc is based on its ability to participate in pentacoordinated derivative formation. Some spectral properties of such a derivative bearing a conformational stabilised zinc-sulfur bond (the sulfur atom belongs to a cysteine residue) are described.     

Synthetic investigations of (1,3′)-bistetrahydroisoquinolines: towards pentacyclic analogues of piperazine core alkaloids

Synthetic investigations of (1,3′)-bistetrahydroisoquinolines are reported as the key intermediates for the synthesis of ecteinascidin and phthalascidin pentacyclic structure analogues through successive Pictet-Spengler cyclization and intramolecular peptide coupling. The direct Pictet-Spengler reaction between a derivative of l-DOPA and N-protected-α-aminoaldehyde was first extended to the synthesis of cis-(1,3′)-bistetrahydroisoquinoline. After introduction of the required amino acid moiety, an efficient six-membered ring intramolecular peptide coupling gave rise to piperazine derivative structures. Complete structural assignments were corroborated by NMR and X-ray spectroscopic methods. Nevertheless, the optical integrity of the N-protected-α-aminoaldehyde seems to be sensitive to the reaction conditions. Pentacylic structures, having an anti C3-C11 backbone stereochemistry, were obtained from cyclization para- and ortho- to the 3-OH group of the l-DOPA derivative.     

Design and synthesis of a novel ring-expanded 4′-thio-apio-nucleoside derivatives

The synthesis of a ring-expanded 4′-thio-apio-nucleoside derivative 4, designed to serve as a potential anti-HIV agent, is described. The epoxy alcohol derivative 10, prepared from 2-butene-1,4-diol, was converted to an allylsulfide derivative 13 in 3 steps. Ring-closing-metathesis of 13 gave the dihydrothiopyran derivative 20, which was further converted into sulphoxide 24. A Pummerer-type thioglycosylation reaction of 24 with a persilylated uracil derivative, followed by conversion to a cytosine derivative and deprotection, gave a racemic mixture of the ring-expanded 4′-thio-apio-nucleoside derivative 4 in good yield.     

Novel synthesis of a unique helical quinone derivative by coupling reaction of 2-hydroxybenzo[c]phenanthrene

Oxidative coupling reaction of both 3-hydroxychrysene and 2-hydroxybenzo[c]phenanthrene by using Cu(NO₃)₂-3H₂O under atmospheric air is described. The former gave the aimed coupled biaryl derivative. However, the latter gave a further oxidized helical quinone derivative. The unique helical structure was characterized by X-ray and NMR analysis.     

Synthesis and structural studies of a novel scaffold for drug discovery: a 4,5-dihydro-3H-spiro[1,5-benzoxazepine-2,4-piperidine]

We describe the three-step synthesis of a novel 4,5-dihydro-3H-spiro[1,5-benzoxazepine-2,4^′-piperidine] scaffold from ortho-hydroxyacetophenone and N-benzylpiperidone. The structure of one disubstituted derivative, studied by NOESY NMR in an aqueous medium and X-ray diffraction, demonstrates that this scaffold presents side chains in a well-defined orientation. The Boc protected derivative represents a key intermediate for the combinatorial synthesis of drug-like molecules.     

Synthesis and odor description of optically active cyclopropanated analogues of geraniol,nerol, nor-leaf alcohol,and matsutake alcohol

Both enantiomers of cyclopropanated analogues of geraniol, nerol, nor-leaf alcohol, and matsutake alcohol were synthesized and their odor properties evaluated. Odor characters in enantiomeric pairs were similar in the geraniol series. The (+)-(2R,3S)-nerol derivative showed various odor aspects. From the results of nor-leaf alcohol derivatives, an interaction between the (2-re,3-re)-face of nor-leaf alcohol and the human olfactory receptor was suggested. The odor of (3R)-matsutake alcohol derivative was superior to the enantiomer.     

The formal synthesis of 3-epi jaspine B using stereoselective intramolecular oxa-Michael addition

The formal synthesis of 3-epi jaspine B was achieved by using a stereoselective intramolecular oxa-Michael addition. The diacetate derivative of 3-epi jaspine B was also synthesized.     

Towards cyclic,conformationally constrained,fluorine-containing β-amino acid derivatives from d-glucose

Novel, potentially bioactive, fluorinated branched-chain monosaccharides were obtained by reaction of diethylaminosulphur trifluoride (DAST) with a series of methyl 3-C-cyano-3-ethoxycarbonyl-β-d-glucopyranoside derivatives, including the 4,6-O-benzylidene derivative and their 3-C-(N-protected aminomethyl) reduction products, as well as the phenyl 3-C-cyano-3-ethoxycarbonyl-1-thio-α-d-(and β-d-)glucopyranosides. The absolute configuration at C(3) was unambiguously assigned for all compounds on the basis of X-ray crystallographic analysis of methyl 4,6-O-benzylidene-3-C-cyano-3-deoxy-3-ethoxycarbonyl-β-d-glucopyranoside, corroborating the previous tentative assignment by other authors for the 4,6-unprotected compound. The course of the fluorination depended on the reaction temperature and the substitution pattern of the substrate. Thus, for methyl 3-C-cyano-3-ethoxycarbonyl-β-d-glucopyranoside, fluorination occurred exclusively at C(6), but for the phenylthio analogue, a 2-deoxy-2-phenylthio-α-d-manno-configured glycosyl fluoride and its 6-fluoro derivative were obtained, resulting from the expected rearrangement reaction, whilst starting from the phenylthio α anomer, only the unrearranged 6-fluoro compound was formed. Rearrangement was also observed in the fluorination of methyl 4,6-O-benzylidene-3-C-(N-protected aminomethyl)-β-d-glucopyranoside, which led to the 2-O-methyl-α-d-mannopyranosyl fluoride derivative as the sole product. This methodology may constitute a simple route to enantiopure conformationally constrained cyclic fluorinated β-amino acids having the α carbon atom shared with a pyranose ring, although only moderate yields were achieved, particularly in the fluorination step.     

Diastereoselective arylation of l-proline derivatives at the 5-position

Diastereoselective introduction of nucleophiles into l-proline derivatives at the 5-position was achieved with suitable selection of N-protecting group. N-Methoxycarbonylated or benzyloxycarbonylated l-proline derivatives reacted with arene to give cis-arylated products. On the other hand, N-benzoylated l-proline derivative preferentially gave trans-arylated product, which could be easily transformed into optically active C₂-symmetrical pyrrolidine derivative. Such derivative 5 worked well as an organic activator in the asymmetric reduction of aromatic imines by Cl₃SiH.     

Synthesis of d-camphor based γ-amino acid (1S,3R)-3-amino-2,2,3-trimethylcyclopentane carboxylic acid

Synthesis of a γ-amino acid derived from (1R,3S)-camphoric acid is described. d-(+)-Camphoric anhydride, prepared from d-(+)-camphoric acid by treatment with methanesulfonyl chloride and triethylamine, was reacted with benzyl alcohol and catalytic DMAP, and subsequently reacted in a Curtius rearrangement to afford the corresponding carbamate derivative. This derivative was converted to the desired γ-amino acid through hydrogenolysis.