Mimicking dihydroxy acetone phosphate-utilizing aldolases through organocatalysis: a facile route to carbohydrates and aminosugars

[reaction: see text] A practical and environmentally friendly organocatalytic strategy designed to mimic the DHAP aldolases has been developed and shown to be effective in the preparation of carbohydrates and aminosugars. (S)-Proline and (S)-2-pyrrolidine-tetrazole catalyzed the aldol reaction between dihydroxy acetone variants such as 1,3-dioxan-5-one and 2,2-dimethyl-1,3-dioxan-5-one with aldehydes to give the corresponding polyols in good yields with very high ees.     

Direct asymmetric organocatalytic de novo synthesis of carbohydrates

A biomimetic organocatalytic asymmetric synthesis of carbohydrates can be accomplished by a proline catalyzed aldol reaction with the dihydroxyacetone equivalent 2,2-dimethyl-1,3-dioxan-5-one and various aldehydes. The biomimetic C₃+C_n strategy directly generates selectively protected carbohydrates in one step, which can be easily deprotected. Additionally, the stereoselective reduction of the keto functions allows a direct entry to different aldopentoses.     

A direct organocatalytic entry to sphingoids: asymmetric synthesis of D-arabino- and L-ribo-phytosphingosine

The organocatalytic asymmetric synthesis of D-arabino- and L-ribo-phytosphingosine is described employing a diastereo- and enantioselective (S)-proline-catalyzed aldol reaction of 2,2-dimethyl-1,3-dioxan-5-one and pentadecanal as the key step.     

Relative tendency of carbonyl compounds to form enamines

Equilibria between carbonyl compounds and their enamines (from O-TBDPS-derived prolinol) have been examined by NMR spectroscopy in DMSO-d(6). By comparing the exchange reactions between pairs (enamine A + carbonyl B → carbonyl A + enamine B), a quite general scale of the tendency of carbonyl groups to form enamines has been established. Aldehydes quickly give enamines that are relatively more stable than those of ketones, but there are exceptions to this expected rule; for example, 1,3-dihydroxyacetone acetals or 3,5-dioxacyclohexanones (2-phenyl-1,3-dioxan-5-one and 2,2-dimethyl-1,3-dioxan-5-one) show a greater tendency to afford enamines than many α-substituted aldehydes.     

环状碳酸酯5,5-二甲基-1,3-二噁烷-2-酮的合成

在三乙胺存在下,2,2-二甲基-1,3-丙二醇和氯甲酸乙酯反应合成了环状碳酸酯5,5-二甲基-1,3-二噁烷-2-酮,其结构经1H NMR和IR表征。提出了可能的反应机理。     

Lessons from nature: biomimetic organocatalytic carbon-carbon bond formations

Nature utilizes simple C2 and C3 building blocks, such as dihydroxyacetone phosphate (DHAP), phosphoenolpyruvate (PEP), and the "active aldehyde" in various enzyme-catalyzed carbon-carbon bond formations to efficiently build up complex organic molecules. In this Perspective, we describe the transition from using enantiopure chemical synthetic equivalents of these building blocks, employing our SAMP/RAMP hydrazone methodology and metalated chiral alpha-amino nitriles, to the asymmetric organocatalytic versions developed in our laboratory. Following this biomimetic strategy, the DHAP equivalent 2,2-dimethyl-1,3-dioxan-5-one (dioxanone) has been used in the proline-catalyzed synthesis of carbohydrates, aminosugars, carbasugars, polyoxamic acid, and various sphingosines. Proline-catalyzed aldol reactions involving a PEP-like equivalent have also allowed for the asymmetric synthesis of ulosonic acid precursors. By mimicking the "active aldehyde" nucleophilic acylations in Nature catalyzed by the thiamine-dependent enzyme, transketolase, enantioselective N-heterocyclic carbene-catalyzed benzoin and Stetter reactions have been developed. Finally, based on Nature's use of domino reactions to convert simple building blocks into complex and highly functionalized molecules, we report on our development of biomimetic asymmetric multicomponent domino reactions which couple enamine and iminium catalysis.     

Efficient cleavage of the N-O bond of 3,6-dihydro-1,2-oxazines mediated by some alpha-hetero substituted carbonyl compounds in mild conditions

The efficient cleavage of the N-O bond of some nitroso Diels-Alder cycloadducts has been achieved in mild conditions, mediated either by 2,2-dimethyl-1,3-dioxan-5-one or 1,3-dithiolane-2-carboxaldehyde. These new and purely organic conditions allow an excellent tolerance with respect to many functional groups that would have been affected by previous reductive cleavage conditions.     

Annulation of beta-aryl-alpha-nitro-alpha,beta-enals and 2,2-dimethyl-1,3-dioxan-5-one: a one-step assembly of nitrocyclitols. Application to a short practical synthesis of (+/-)-7-deoxy-2-epi-pancratistatin tetraacetate

A novel, highly stereocontrolled formal [3 + 3] annulation of beta-aryl-alpha-nitro-alpha,beta-enals with the enamine derived from 2,2-dimethyl-1,3-dioxan-5-one and pyrrolidine afforded protected nitrocyclitols with five newly created stereocentres and constituted the key step in a short, gram-scale synthesis of a pancratistatin analogue.     

Lactam and amide acetals. 52. Reaction of dimethylformamide diethylacetal with 2,2-dimethyl-4,6-dioxo-1,3-dioxane (Meldrum's acid)

Depending on the conditions of carrying out the reaction of dimethylformamide diethylacetal with the Meldrum's acid, either 2,2-dimethyl-4,6-dioxo-5-(N,N-dimethyl-aminomethylene)-1,3-dioxane or N,N,N¹N¹-tetramethylformamidinium salt of 2,2-dimethyl-4,6-dioxo-5-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)methylene-1,3-di-oxane are formed. The two compounds can react with primary amines to form N-substituted 2,2-dimethyl-4.,6-dioxo-5-aminomethylene-1,3-dioxanes.For Communication 51, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 184–187, February, 1988.     

Preparative synthesis of 2,2-dimethyl-5-(trifluoroacetyl)-1,3-dioxane-4,6-dione (2-trifluoroacetyl Meldrum's acid) and 2,2-dimethyl-6-(trifluoromethyl)-4H-1,3-dioxin-4-one and their synthetic usefulness as (trifluoroacetyl)ketene precursors

A simple and reliable method for the preparation of 2,2-dimethyl-5-(trifluoroacetyl)-1,3-dioxane-4,6-dione and 2,2-dimethyl-6-(trifluoromethyl)-4H-1,3-dioxin-4-one on a multigram scale was developed. These (trifluoroacetyl)ketene precursors were used in the hetero-Diels-Alder reaction with dialkylcyanamides and 1-ethoxyprop-1-yne, as well as in some reactions with nucleophiles.     

Asymmetric synthesis of (+)-altholactone: a styryllactone isolated from various Goniothalamus species

The asymmetric total synthesis of (+)-altholactone (1), a member of the styryllactone family of natural products displaying cytotoxic and antitumor activities, is described. Key steps include a RAMP-hydrazone alpha-alkylation (RAMP=(R)-1-amino-2-methoxymethylpyrrolidine) of 2,2-dimethyl-1,3-dioxan-5-one, a boron-mediated aldol reaction, a six- to five-membered ring acetonide shuffling, an oxidative 1,5-diol to delta-lactone conversion and a stereoselective ring-closure to generate the annulated tetrahydrofuran moiety with inversion of configuration.     

A new tetrazole-containing 2-amino-4,6-di(aziridin-1-yl)-1,3,5-triazine derivative: synthesis,interaction with DNA,and antitumor activity

Russian Chemical Bulletin - ({5-[4,6-Di(aziridin-1-yl)-1,3,5-triazin-2-yl]amino}-2,2-dimethyl-1,3-dioxan-5-yl)-methyl 2-(5-phenyl-2H-tetrazol-2-yl)acetate was synthesized and characterized. The...     

Aliphatic α-nitroalkyl-<Emphasis Type="Italic">ONN</Emphasis>-azoxy compounds and their derivatives

Interaction of primary amines and 2,2-dimethyl-5-nitro-5-nitroso-1,3-dioxane in the presence of dibromoisocyanurate generates 2,2-dimethyl-5-nitro-1,3-dioxan-5-yl-ONN-azoxyalkanes. Based on the reaction of the latter with AcCl/MeOH followed by further transformations, the first representatives of mononitro- and polynitroalkyl-ONN-azoxyalkanes, i.e., (methyl-NNO-azoxy)nitromethane and dinitro(methyl-NNO-azoxy)methane, as well as some their derivatives, were prepared.     

A simple synthesis of 2,4-diaryl-1,3,5-triazines

Summary Arylamidines2 react with 5-methoxymethylen-2,2-dimethyl-1,3-dioxan-4,6-dione5 to give 2,4-diaryl-1,3,5-triazines in moderate to good yields.5 can be comprehended as a formic acid derivative which transfers a C₁-building block. Other formic acid derivatives give only poor to moderate yields of triazines by treatment with amidines. The synthetic method is applicable to aromatic amidines.

---

Eine einfache Synthese von 2,4-Diaryl-1,3,5-triazinen

Zusammenfassung Die Arylamidine2 reagieren mit 5-Methoxymethylen-2,2-dimethyl-1,3-dioxan-4,6-dion5 in guten Ausbeuten zu 2,4-Diaryl-1,3,5-triazinen. Verbindung5 kann als Derivat der Ameisensäure aufgefaßt werden, welches einen C₁-Baustein überträgt. Andere Derivate der Ameisensäure ergeben bei Umsetzung mit Amidinen nur schlechte Ausbeuten an Triazinen. Die beschriebene Methode ist auf aromatische Amidine anwendbar.

     

A concise route to (+)-lactacystin

A facile chromatography-free route to Kang's intermediate for the synthesis of (+)-lactacystin, a potent proteasome inhibitor, has been developed starting with Brown's asymmetric crotylation of tert-butyl 5-formyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate, easily available from 2-amino-2-(hydroxymethyl)propane-1,3-diol (Tris).     

A Convenient Synthesis of 3- and 3,4-Substituted 4,5-Dihydroisoxazole-5-Acetic Acids

The 4,5-dihydroisoxazole-5-acetic acids 4a-j were prepared from the ketoximes 1a-j, 2,2-dimethyl-5-methoxymethylene-1,3-dioxan-4,6-dione (2) and butyllithium in yields from 35 to 79%.     

Study of Nitrogen- and Sulfur-Containing Heterocycles. 57. Synthesis and Conversion of 4′-Substituted 5-(5-Amino-6-Pyrimidylthio)-2,2-Dimethyl-4,6-Dioxo-1,3-Dioxanes

By reaction of 4-substituted 5-amino-6-mercaptopyrimidines with 5-bromo-2,2-dimethyl-4,6-dioxo-1,3-dioxane, we have obtained 4′-substituted 5-(5-amino-6-pyrimidylthio)-2,2-dimethyl-4,6-dioxo-1,3-dioxanes. We have studied diazotization of these compounds by isoamyl nitrite. In the case of 4′-methoxy- and 4′-dimethylamino-substituted derivatives, we have obtained derivatives of novel heterocyclic systems: pyrimido[5,4-e][1,3,4]thiadiazine and pyrimido[5,4-e][1,3,4]thiadiazine-7-spiro-5′-1,3-dioxane, and in the case of the 4′-isopropylamino-substituted derivative we obtained 4-isopropyl-7-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)-1,2,3-triazolo[5,4-d]pyrimidin-7-ylidene.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 613–623, April, 2005.     

Synthesis and characterization of benzodioxinone mono-telechelics and their use in block copolymerization

Poly(methyl methacrylate) (PMMA) and poly(ethylene glycol) methyl ether (mPEG)-based monotelechelics were quantitatively prepared by copper (I)-catalyzed azide/alkyne cycloaddition (CuAAC) click reactions using azido-terminated polymers and alkyne functional benzodioxinones. The monotelechelic containing dimethyl moities (2,2-dimethyl-5-(prop-2-yn-1-yloxy)-4H-benzo[d][1,3]dioxin-4-one) was heat-sensitive, whereas the monotelechelic containing diphenyl moieties (2,2-diphenyl-5-(prop-2-yn-1-yloxy)-4H-benzo[d][1,3]dioxin-4-one) was UV light sensitive. Based on the FT-IR, ¹H-NMR, and GPC investigations, the CuAAC click reactions enable the quantitative syntheses of monotelechelics under mild conditions. Moreover, the photosensitive mPEG-based monotelechelic was further utilized for the block copolymer synthesis upon UV-light irradiation. The photoinduced acylation of mPEG monotelechelic consist of (2,2-diphenyl-5-(prop-2-yn-1-yloxy)-4H-benzo[d][1,3]dioxin-4-one) in the presence of hydroxy-terminated poly(epsilon caprolactone) enabled the successful block copolymer formation.     

无外加催化剂条件下芳香醛与活性亚甲基化合物的缩合反应和迈克尔加成反应

在DMF溶剂中，不外加催化剂使芳香醛(1)与2,2-二甲基-1,3-二氧六环-4,6-二酮(2)发生缩合反应生成2,2-二甲基-5-芳亚甲基-1,3-二氧六环-4,6-二酮(3a～f)。在同样条件下，芳香醛与5,5-二甲基-1,3-环己二酮(4)则发生缩合和迈克尔加成反应生成2,2'-芳亚甲基双(3-羟基5,5-二甲基-2-环己烯-1-酮)(5a～h)。用单晶X-射线分析法确定了产物5b的晶体结构。     

Facile syntheses of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones and the corresponding 6-substituted 4-hydroxy-2-pyrones

A variety of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones 5a-l and the corresponding 6-substituted 4-hydroxy-2-pyrones 3a-l were prepared in high yields under mild reaction conditions by the reaction of 2,2,6-trimethyl-1,3-dioxin-4-one 4 with 1-acylbenzotriazoles 9 in the presence of LDA followed by thermal cyclization of 5a-l to 3a-l. Synthesis of novel 6-(1-benzoylalkyl)-2,2-dimethyl-1,3-dioxin-4-ones 12a-c was achieved by alkylation of dioxinone 5a and their subsequent cyclization gave 5-alkyl-4-hydroxy-2-pyrones 13a-c.