Reaction of 2-bromomethylazoles and TosMIC: A domino process to azolopyrimidines. Synthesis of core tricycle of the variolins alkaloids

A new reaction of N-protected 2-bromomethylazoles and tosylmethyl isocyanide (TosMIC) leading to the preparation of azolopyrimidines is described. This domino sequence was used to synthesize the pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine core of alkaloids variolins from 4-methoxy-2-methylpyrrolo[2,3-b]pyrimidine in two steps.     

Heterocyclizations with tosylmethyl isocyanide derivatives. A new approach to substituted azolopyrimidines

An efficient synthesis of substituted azolopyrimidines such as pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidines, pyrimido[1,6-a]indoles, benzo[4,5]imidazo-[1,2-c]pyrimidines, an imidazo[1,2-c]pyrimidine, and pyrazolo[1,5-c]pyrimidines is described. The method involves the reaction of N-protected bromomethylazoles and tosylmethyl isocyanide (TosMIC) derivatives in nonanhydrous media. The study of the reaction conditions shows that the method is only successful under phase-transfer conditions (CH2Cl2/30% aq NaOH) using benzyltriethylammonium chloride as a catalyst.     

Enantioselective total synthesis of marine alkaloids,manzamine A and related compounds

A review of our studies toward the enantioselective total synthesis of ircinal A, manzamine A and related compounds is presented in detail.     

Enantioselective strategy to the spirocyclic core of Palau'amine and related bisguanidine marine alkaloids

[structure: see text] An enantioselective strategy to the spirocyclic core found in the oroidin-derived family of bisguanidine marine alkaloids has been devised, premised on a biosynthetic proposal. Herein, we describe the successful implementation of this strategy, which entails a Diels-Alder reaction and a chlorination/ring contraction sequence that delivers the fully functionalized spirocyclic core. In this initial report, an intermolecular chlorination delivers a cyclopentane that is epimeric at C17 relative to the palau'amines and epimeric at C11 relative to the axinellamines.     

1-Methylimidazole-catalyzed reaction between tosylmethyl isocyanide and dialkyl acetylenedicarboxylates:An efficient synthesis of functionalized pyrroles

An efficient 1-methylimidazole-catalyzed synthesis of dialkyl 2-[(4-methylphenyl)sulfonyl]-1H-pyrrole-3,4-dicarboxylates is described.The reactive 1:1 zwitterionic intermediate formed by the addition of 1-methylimidazole to dialkyl acetylenedicarboxylates is trapped by tosylmethyl isocyanide(TOSMIC) to afford the title compounds in excellent yields.     

A novel straightforward synthesis of enantiopure tetrahydroisoquinoline alkaloids.

A novel, direct,and high-yielding stereoselective method for enantiopure 1-substituted tetrahydroisoquinolines (THIQ) is described. The successful approach, which creates the stereocenter during the formation of the THIQ nucleus is based on (i) formation of chiral 2,3-substituted perhydro-1,3-benzoxazines derived from (-)-8-aminomenthol, (ii) diastereoselective intramolecular ring opening of the N,O-acetal moiety by an arylmetal generated from the substituent at the nitrogen atom in the perhydrobenzoxazine ring, and (iii) removal of the chiral auxiliary appendage. The starting perhydrobenzoxazines are easily prepared from (-)-8-aminomenthol and two different aldehydes, and the intramolecular opening is stereospecific, leading to a single stereoisomer. The method allows the preparation of a wide variety of enantiopure 1-substituted THIQ, with different substituents at C-1, by changing the nature of the starting aldehydes.     

A novel synthetic approach for the synthesis of pyridocarbazole alkaloids

The synthesis of 11‐methyl‐6H‐pyrido[4,3‐b]carbazole‐1(2H)‐one (5), which can be important for the synthesis of other pyridocarbazole alkaloids and especially 1‐substituted ellipticines, is described. Construction of the tetracyclic structure was achieved by a new route and two important precursor compounds (4a and 4b) for the synthesis of pyridocarbazole alkaloids and also many new tetrahydrocar‐bazole derivatives (7, 8, 9, 10, 11, 12, 13) were synthesized.     

One-step synthesis of 3-aryl- and 3,4-diaryl-(1H)-pyrroles using tosylmethyl isocyanide (TOSMIC)

A one-step synthesis of 3-aryl and 3,4-diaryl-(1H)-pyrroles from TOSMIC and commercially available or readily synthesized arylalkenes is reported. Optimal conditions were found to be NaOtBu in DMSO. The methodology was particularly efficient (yields > 65%) when electron poor aryl groups were attached to the alkene.[ reaction: see text]     

A novel and versatile method for the enantioselective syntheses of tropane alkaloids

A full account of the novel and flexible approach to hydroxylated 8-azabicyclo[3,2,1]octan-3-ones and 9-azabicyclo[3,3,1]nonan-3-ones is presented.Using keto-lactams as the starting materials,this two-step method consists of silyl enol ether formation with TBDMSOTf,lactam activation with Tf2O/DTBMP,and halide-promoted cyclization.Radical dechlorination of the resulting 1-halotropan-3-ones led to the corresponding hydroxylated tropan-3-ones,which can be hydrogenated to yield3,6-dihydroxytropanes.Starting from optically active keto-lactams,the method has been applied to the enantioselective syntheses of(+)-(1S,3S,5R,6S)-pervilleine C(6),(+)-(1S,3R,5S,6R)-valeroidine(3),(+)-(1S,3S,5R,6S)-dibenzoyloxytropane(8),and(+)-(1S,3S,5R,6S)-merredissine(9).     

Chiroptical analysis of marine sponge alkaloids sharing the pyrrolopyrazinone core

A systematic experimental study has been conducted on the chiroptical properties of bi‐ and tricyclic pyrrolopyrazinones, which occur as the core in a variety of marine pyrrole–imidazole alkaloids, such as the immunosuppressive palau'amine. On the basis of the chiral‐pool synthesis of conformationally fixed dipyrrolopyrazinones, it was possible to predict the CD spectrum of (?)‐dibromophakellin above 240 nm. 2,2,2‐Trifluoroethanol was identified as a superior solvent for this analysis. Positive Cotton effects at 250 nm can be used to determine the helicity of dibrominated pyrrolopyrazinones, while the intensity of the Cotton effect at 285 nm is governed by the relative stereochemistry. The influence of bromination of the pyrrole ring also becomes predictable. One of the tricycles can be considered as “conformationally frozen longamide A”. Our study also gives the first comparative Röntgen analyses of diastereomeric Mosher esters of N,O‐hemiacetals, with the results underlining the fact that caution is advised in the application of the advanced Mosher method.     

The synthesis of compounds related to the indole-indoline core of the vinca alkaloids (+)-vinblastine and (+)-vincristine

A series of α′-aryl-α′-carbomethoxycycloalk-2-en-1-ones, 16, has been prepared using the Pinhey arylation methodology for introducing the aromatic residue. Subjection of these compounds to Johnson iodination and Pd[0]-catalyzed Ullmann cross-coupling of the resulting α-iodocycloalkenones 11 with 2-iodonitrobenzene (5, X = I) then affords α,α′-diaryl-α′-carbomethoxycycloalk-2-en-1-ones of the general form 10. Reductive cyclization of this last type of compound gives the corresponding indoles 9a-f (n = 1-3), some of which resemble the indole-indoline cores of the clinically important alkaloids (+)-vinblastine (1) and (+)-vincristine (2).     

A novel method for the synthesis of dichloroalkenes

A novel convenient method for the synthesis of dichloroalkenes was developed. The method involves catalytic olefination of hydrazones of aliphatic carbonyl compounds with bromo(trichloro)methane.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2538–2540, November, 2004.     

A novel method for the synthesis of maxacalcitol

Maxacalcitol (1), a kind of active vitamin D drugs, was prepared from pregnenolone acetate (2) using a novel synthetic method including the combination of five-step organic transformations and one-step biological transformation. The new protocol was shorter, milder, and simpler than the reported approaches. The unoptimized overall yield was 0.178%. The structure of all intermediates and final product was confirmed by ¹H NMR, ¹³C NMR and MS techniques.     

合成二苄基二硒醚的新方法

苯骈三氮唑和胺(伯、仲胺: 芳胺、杂环胺或杂环芳胺)、苯甲醛发生Mannich反应, 生成N-取代-1-苯骈三氮唑基苄胺, 它与硒氢化钠反应生成二苄基二硒醚, 反应条件温和, 产率高, 胺和苯骈三氮唑均可回收再利用。     

Asymmetric synthesis of the azabicyclic core of the Stemona alkaloids

A general strategy for the construction of the 1-azabicyclo[5.3.0]decane core of Stemona alkaloids is developed. Our diversity-oriented approach exploits 1,3-dipolar cycloaddition of five-membered cyclic nitrones to C(6) olefins, followed by N-O reductive cleavage and azepine closure. The use of various enantiopure pyrroline N-oxides allows for a practical, stereoselective preparation of several putative precursors of different Stemona alkaloids.     

A facile synthesis of bispyrroloquinone and bispyrroloiminoquinone ring system of marine alkaloids

Bispyrroloquinone and bispyrroloiminoquinone are two important polycyclic ring systems present in biologically active marine alkaloids such as Zyzzyanones, tsitsikammamines, and wakayin. A facile synthesis of these two ring systems starting from a 6-benzylamino indole-4,7-quinone or 6-benzylamino pyrroloiminoquinone is described here. This chemistry involves the construction of a pyrrole ring in a single step by treatment of the starting reagents with ethyl acetoacetate or phenylbutane-1,3-dione in the presence of ceric ammonium nitrate in MeOH/CH₂Cl₂ solvent.