Novel synthesis of 4-chloro-3-hydroxy-2-pyrone by the reaction of acetonide protected 4,5-dihydroxy-2-chloroglycidic ester with magnesium chloride

Treatment of acetonide protected 4,5-dihydroxy-2-chloroglycidic ester with magnesium chloride gave 4-chloro-3-hydroxy-2-pyrone in excellent to good yields.     

Novel synthesis of the ortho ester derivative of 4,5-epoxymorphinan

[reaction: see text]. A method was found for the novel synthesis of ortho ester derivatives that are potentially useful as selective epsilon opioid receptor ligands. An unexpected 17-(cyclopropylmethyl)-4,5alpha-epoxy-6alpha-hydroxy-3,7,7-trimethoxy-8-oxa-6,14-endoethanomorphinan was produced when 17-(cyclopropylmethyl)-4,5alpha-epoxy-3-methoxy-6alpha,14-dihydroxy-6beta-(1,3-dithia-2-yl)-morphinan was treated in methanol with trimethyl orthoformate and CuO/CuCl2. This ortho ester derivative was then converted to an ester with acid. The structure of the ortho ester was determined by 2D NMR (HMBC) and mass spectra.     

Synthesis of (R)-(+)-tanikolide through stereospecific C-H insertion reaction of dichlorocarbene with optically active secondary alcohol derivatives

Stereospecific alpha C-H insertion reaction of protected chiral 1,2-glycols, (S)-1,2-isopropylidenedioxytridecane (3) and ethyl (S)-4,5-isopropylidenedioxy-pentanoate (4), prepared from (R)-glyceraldehyde acetonide (2), with dichlorocarbene generated from CHCl(3)/50% NaOH/cetyltrimethylammonium chloride (as ptc.) took place with complete retention of configuration to provide (S)-4-dichloromethyl-2,2-dimethyl-4-undecyl-1,3-dioxolane (5) and ethyl (S)-3-(4-dichloromethyl-2,2-dimethyl-1,3-dioxolan-4-yl)-propanoate (8), respectively. The ester (8) was transformed to 5 by elongation of the side chain. The glycol derivative (5) was converted into O-TBDPS-protected (S)-2-hydroxymethyl-2-undecyloxirane (16). Reaction of 16 with a cuprate reagent containing homoallylic carbon chain followed by oxidative manipulation of the terminal olefin afforded (R)-(+)-tanikolide (1).     

Synthesis of (R)-2-methyl-4-deoxy and (R)-2-methyl-4,5-dideoxy analogues of 6-phosphogluconate as potential inhibitors of 6-phosphogluconate dehydrogenase

The synthesis of (2R)-2-methyl-4,5-dideoxy and (2R)-2-methyl-4-deoxy analogues of 6-phosphogluconate is described. The synthetic strategy relies on the Evans aldol reaction for the installation of the chiral centres in the 2- and 3-positions. The selective phosphorylation at the primary alcohol function of (2R,3S)-3,6-dihydroxy-2-methylhexanoic acid benzyl ester (5) and (2R,3S,5S)-3,5,6-trihydroxy-2-methylhexanoic acid benzyl ester (20) was achieved with dibenzyl phosphochloridate and dibenzyl phosphoiodinate respectively, working at low temperature. (2R,3S)-3-Hydroxy-2-methyl-6-phosphonoxyhexanoic acid (9) was obtained in 25% overall yield from 4-benzyloxybutanol and (2R,3S,5S)-3,5-dihydroxy-2-methyl-6-phosphonoxyhexanoic acid (28) in 10% overall yield from L-malic acid.     

Synthesis of 5,6-dihydroxy-2-phenyl-4-pyrimidinecarboxylic acid,methyl ester,a corrected structure

Pyrolysis of the adduct of benzamide oxime and dimethyl acetylenedicarboxylate leads to 5,6-dihydroxy-2-phenyl-4-pyrimidinecarboxylic acid methyl ester ( 4a ) rather than 4,5-dihydro-α,4-dioxo-2-phenyl-1H-imidazole-5-acetic acid, methyl ester ( 1 ).     

Synthesis of P1 aspartate-based peptide acyloxymethyl and fluoromethyl ketones as inhibitors of interleukin-1β-converting enzyme

Improved procedures have been developed for the synthesis of P1 aspartate-based 2,6-dichlorobenzoyloxymethyl ketone 1 and fluoromethyl ketone 2, the prodrugs of two potent ICE-inhibitors. 1 was prepared from (R)-trans-4,5-O-isopropylidene-4,5-dihydroxy-2-pentenecarboxylic acid ethyl ester; 2 was obtained via a nitro-aldol condensation as key step from in situ generated fluoroacetaldehyde.     

Stereoselective synthesis of a new trihydroxyindolizidine lactone

A general approach to 1,6,7-trihydroxyindolizidin-8-carboxylates is illustrated through the synthesis of a γ-lactone in an enantiopure form in seven steps starting from (3S)-3-t-butyloxy-1-pyrroline N-oxide and the acetonide of (2E,4S)-4,5-dihydroxy-2-pentenoic acid derived from (S)-malic acid and mannitol, respectively. The process was completely stereoselective and allowed the total control of the relative and absolute configuration of the five contiguous stereocentres of the product.     

Further Syntheses of Optically Active Verrucarinic Acid, 43rd Communication of Verrucarins and Roridins

Two new syntheses of verrucarinic acid (2S, 3R-dihydroxy-3-methylpentanoic acid) and its derivatives, suitably protected for the further conversion to macrocyclic trichothecenes, are described. The first one makes use of a diastereoselective alkylation of a (?)-(S)-malic acid ester and the regioselective reductin of one carboxyl function toa methyl group. The second approach involves a stereoselective addition of an allylsilane to a chiral glyoxylate.     

Reactions of alkyl 2-benzylidene-2-polyfluoroacylacetates with N,N-dinucleophiles

Alkyl 2-benzylidene-2-polyfluoroacylacetates react with urea and thiourea to yield 5-ethoxycarbonyl-4-fluoroalkyl-4-hydroxy-6-phenylhexahydropyrimidin-2-ones and -2-thiones and with guanidine sulfate to form 2-amino-5-ethoxycarbonyl-4-fluoroalkyl-6-phenyl-1,6-dihydropyrimidines and 3,6-diethoxycarbonyl-2,7-difluoroalkyl-4,5-diphenyl-4,5-dihydro-1H-pyrido[1,2-a]pyrimidines, and they react with phenylhydrazine to afford 4-alkoxycarbonyl-3-fluoroalkyl-3-hydroxy-1,5-diphenylpyrazolidines. Hydrazine hydrate catalyzes the formation of 3,5-diethoxycarbonyl-2,6-difluoroalkyl-2,6-dihydroxy-4-phenyltetrahydropyrans. When treated with anhydrous hydrazine and o-phenylenediamine, these esters cleave to form the products of condensation of fluoroacyl ester and benzaldehyde with diamines.     

Syntheses of Optically Active Verrucarinic Acid. 40th Communication on Verrucarins and Roridins

Three syntheses of (2S, 3R)-2,5-dihydroxy-3-methylpentanoic acid (verrucarinic acid) and its derivatives suitably protected for the further transformation to macrocyclic trichothecenes are described. These involve an enantioselective ester hydrolysis by pig liver esterase, a Sharpless epoxidation and an asymmetric hydroboration.     

Efficient synthesis of cis- and trans-3,4-dihydroxy-3,4-dihydromollugin

An efficient synthesis of naturally occurring compounds isolated from Pentas longiflora, cis-3,4-dihydroxy-3,4-dihydromollugin 2, and trans-3,4-dihydroxy-3,4-dihydromollugin 3 is described. The O-protected mollugins were dihydroxylated using OsO4 to achieve the corresponding cis-dihydroxy derivatives in excellent yield. The synthesis of trans-3,4-dihydroxy-3,4-dihydromollugin was achieved using Oxone in good yield. A mechanism for the formation of cis-3,4-dihydroxymollugin acetonide from the reaction of mollugin with Oxone is proposed.     

Porphyrins with exocyclic rings. Part 24. Synthesis and spectroscopic properties of pyrenoporphyrins, potential building blocks for porphyrin molecular wires

Porphyrins with fused pyrene units have been prepared by ‘2+2’ and ‘3+1’ methodologies. Nitration of 1,2,3,6,7,8-tetrahydropyrene, followed by oxidation with DDQ, gave 4-nitropyrene and this condensed with ethyl isocyanoacetate in the presence of DBU or a phosphazene base to generate a pyrenopyrrole ethyl ester. Ester saponification and decarboxylation with KOH in ethylene glycol at 190 °C gave the parent pyreno[4,5-c]pyrrole and this was further condensed with 2 equiv of acetoxymethylpyrroles to afford the corresponding tripyrranes protected at the terminal positions with tert-butyl esters. In a one pot procedure, the ester protective groups were cleaved with TFA and following dilution with dichloromethane, ‘3+1’ condensation with a pyrrole dialdehyde, and dehydrogenation with DDQ, the targeted pyrenoporphyrins were generated in good overall yields. A dialdehyde was also prepared from the pyrenopyrrole intermediate and this reacted to give an opp-dipyrenoporphyrin. The pyrenopyrrole ethyl ester reacted with dimethoxymethane in the presence of an acid catalyst to give a dipyrenopyrrolylmethane, and this was used to prepare an adj-dipyrenoporphyrin using the MacDonald ‘2+2’ approach. The pyrenopyrrole dialdehyde was also used to prepare a porphyrin with fused pyrene and phenanthroline moieties. Although the UV-vis spectra of these new porphyrin systems are unexceptional, pyrenoporphyrins show many of the features necessary for the construction of porphyrin molecular wires.     

One‐Pot Substitution‐Rearrangement Reaction of 2‐Chloroglycidic Ester: Effective Protocol for the Preparation of 3‐Arylsulfenyl‐2‐keto Ester

The one‐pot substitution‐rearrangement reaction of 2‐chloroglycidic ester is reported. Treatment of 2‐chloroglycidic ester with sodium arylthiolate at room temperature results in the formation of 3‐arylsulfenyl‐2‐keto ester in excellent to good yields.     

Novel route of the reaction of trifluoromethyl-containing N-methyl(4-ethoxyphenyl)imidazolidin-2-ones with urea

The reactions of perfluorobiacetyl with N-(4-ethoxyphenyl)- and N-methylurea afforded cis- and trans-isomers of 1-methyl-4,5-dihydroxy-4,5-bis(trifluoromethyl)imidazolidin-2-one and 1-(4-ethoxyphenyl)-4,5-dihydroxy-4,5-bis(trifluoromethyl)imidazolidin-2-one in a yield of ～60—75%. N-Alkyl(aryl)bis(trifluoromethyl)imidazooxazoles were obtained as unexpected products in the reaction of 1-alkyl(aryl)-4,5-dihydroxy-4,5-bis(trifluoromethyl)imidazolidin-2-ones with urea in dimethylacetamide. The reaction is accompanied by the rearrangement of imidazolidin-2-ones to N-alkyl(aryl)-5,5-bis(trifluoromethyl)hydantoins with CF₃ group migration from position 5 to position 4 of the starting heterocycle. A similar rearrangement is observed on boiling of the studied imidazolidin-2-ones in dimethylacetamide. The molecular structures of 3-(4-ethoxyphenyl)-5,5-bis(trifluoromethyl)imidazolidine-2,4-dione and 6-(4-ethoxyphenyl)-3a,6a-bis(trifluoromethyl)tetrahydroimidazo[4,5-d]oxazole-2,5-dione were studied by X-ray diffraction analysis.     

A method for the synthesis of racemic and optically active 2-substituted 9-(2′,3′-dihydroxypropyl)-8-azahypoxanthines and 8-azaadenines

Several 9-(2′,3′-O-isopropylidene)- and 9-(2′,3′-dihydroxypropyl)-8-azahypoxanthines and 8-azaadenines were synthesized by a “one pot” method starting from the acetonide of racemic or (S)-1-azido-2,3-dihydroxypropane, obtained from D-mannitol. 9-(2′,3′-Dihydroxypropyl)-8-azapurines were tested as adenosine deaminase inhibitors.     

由5-噁唑烷酮合成二肽类的简便方法(英文)

用一锅法制得了２－三溴甲基－３－甲酰基－４－甲基－５－氧－口恶唑烷酮,它与脯氨酸甲酯及其它氨基酸酯反应生成Ｎ－甲基－Ｌ－丙氨酰脯氨酸甲酯和系列Ｎ－甲基－Ｌ－丙氨酰的二肽     

α-Thioureidoalkylation of functionally substituted ureas: II. Synthesis of thio analogs of N-hydroxyalkyl-1,5-diphenylglycolurils

Reactions of N-(hydroxyalkyl)ureas with 4,5-dihydroxy-4,5-diphenylimidazolidine-2-thiones gave previously unknown 4,6-dialkyl-1-hydroxyalkyl-3a,6a-diphenyl-5-thioxooctahydroimidazo[4,5-d]imidazol-2-ones which may be regarded as thio analogs of N-(hydroxyalkyl)glycolurils.     

The first stereoselective total synthesis of nicotlactone A

Herein we report the first stereoselective total synthesis of nicotlactone A via acid catalyzed acetonide deprotection followed by intramolecular lactonization in one pot as the key step.     

Breakdown of Chlorophyll: Partial synthesis of a putative intermediary catabolite. Preliminary communication

The partial synthesis of 10,22-dihydro-4,5-dioxo-4,5-secopheophorbide a ( 1 ) from pheophorbide a methyl ester (2) is described. A regioselective, photooxygenolytic reaction of (pheophorbidato a methyl ester)cadmium(II)( 3 ) provides the entry to the crucial 4,5-secoporphinoid structure in form of the (10,22-dihydro-4,5-dioxo-4,5-seco-pheophorbidato a methyl ester)cadmium(II) ( 4 ). The hydride reduction of this 4,5-dioxo-4,5-secophytoporphyrin ester occurs selectively at the ‘eastern’ meso-position to lead (after demetallation) to 10,22-dihydro-4,5-dioxo-4,5-secopheophorbide a methyl ester ( 5 ). This oxobilin-carbaldehyde has the structure assigned earlier to an ester of an isolation form of the red pigment(s) from Chlorella protothecoides. Hydrolysis of the propanoate ester function of 5, selectively catalyzed by pig liver esterase, then yields the title compound 1 . The red tetrapyrrole 1 may represent an intermediary chlorophyll catabolite in degreening plants.     

One‐Pot Synthesis of 2‐Substituted 4‐Aryl‐4,5‐dihydro‐3,1‐benzoxazepines from 2‐(2‐Aminophenyl)‐1‐arylethanols via Dehydration of the Corresponding Amides

An efficient method for the preparation of 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepine derivatives under mild conditions has been developed. The reaction of 2‐(2‐aminophenyl)ethanols 1 with acid chlorides in the presence of excess Et₃N in THF at room temperature gave the corresponding N‐acylated intermediates 2 , which were dehydrated by treatment with POCl₃ to give 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepines 3 in a one‐pot reaction.