Efficient kinetic resolution of (±)-1,2-O-isopropylidene-3,6-di-O-benzyl-myo-inositol with the lipase B of Candida antarctica

(±)-1,2-O-Isopropylidene-3,6-di-O-benzyl-myo-inositol is a relevant starting material in the synthesis of inositol phosphates and their analogs. In this study, we disclose our efforts toward an efficient methodology for the kinetic resolution of this compound by lipase B of Candida antarctica (Novozym 435). This reaction selectively affords L-(?)-1,2-O-isopropylidene-5-O-acetyl-3,6-di-O-benzyl-myo-inositol. From a conversion of 34% with EtOAc as an acylating agent, the use of vinyl acetate increased the yield to over 49%, while maintaining a very high ee (>99%). The combination of the latter reagent with TBME as a solvent accelerates the reaction.     

Regioselectivity in the reductive ring-opening reaction of 1,2-O-benzylidene sugars

Regioselectivity in the ring-opening reaction of 1,2-O-benzylidene sugars was studied. In the reductive ring-opening reaction of 1,2-O-benzylidene derivatives, only a CO1 bond was cleaved in the case of manno-type, but both the CO1 and CO2 bonds were cleaved in the case of gluco-type.     

A short and common stereoselective approach to 5/6, 6/6, 6/7 bicyclic aza sugars

An efficient and highly stereoselective approach to bicyclic aza sugars is described using Grignard reaction on an N-benzyl imine derived from 3-O-benzyl-1,2-O-isopropylidine-α-d-xylo-pentodialdofuranose, ring closing metathesis, and reductive cyclization as key steps.     

Stereoselective total synthesis of (+)-cardiobutanolide and (+)-3-epi-cardiobutanolide from diacetone d-glucose

A chiron approach starting with 3-O-benzyl-1,2-O-isopropylidene-α-d-xylo-pentodialdo-1,4-furanose utilizing a Grignard reaction, Mitsunobu stereoinversion, ethyl diazoacetate addition, and selective reduction of the ketone is employed as a key step for the total synthesis of (+)-cardiobutanolide described; a similar strategy is also reported for the first total synthesis of (+)-3-epi-cardiobutanolide.     

A photo-induced fluorogenic reaction for the detection of catecholamine-O-sulfates

Catecholamine-O-sulfates react with 1,2-diaminoethane to give fluorescent products if exposed to u.v. irradiation (312 nm) in the presence of oxygen. The fluoresence spectra of the reaction mixtures are similar to those obtained form the fress catecholamines and diaminoethane, indicating that the reaction proceeds by photo-cleavage of the O-sulfate bond, followed by reaction of the free catecholamine withdiaminoethane and oxygen. The factors that affect the reaction are described. After a 40-min irradiation of the catecholamine-O-sulfates in 0.71 M diaminoethane solution at 7°C, the intensities compared to those generated from free catecholamines were 46% for dopamine-3-O-sulfate, 84% for dopamine-4-O-sulfate, 42% for norepinephrine-3-O-suflate, 50% for nonrepinephrine-4-O-sulfate, 64% for epinephrine-3-O-sulfate and 136% for epinephrine-4-O-sulfate.     

Characterisation and properties of new ionic liquids with the difluoromono[1,2-oxalato(2-)-O,O′]borate anion

Three ionic liquids with borate anions of low symmetry, tetraethylammonium difluoromono[1,2-oxalato(2-)-O,O′]borate, 1-ethyl-3-methylimidazolium difluoromono[1,2-oxalato(2-)-O,O′]borate, and 1-butyl-3-methylimidazolium difluoromono[1,2-oxalato(2-)-O,O′]borate were synthesised and characterised by physicochemical and electrochemical measurements including thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), cyclic voltammetry (CV), viscosity and conductivity measurements.     

Asymmetric Baylis–Hillman reaction using sugar acrylates—synthesis of optically active α-methylene-β-hydroxy alkanoates

A study on the asymmetric Baylis–Hillman reaction of three chiral acrylates; 1,2:5,6-di-O-iso-propylidine-α-d-glucofuranose-3-acrylate 1, 2,3:5,6-di-O-iso-propylidine-α-d-mannofuranose-1-acrylate 2 and 1,2-O-iso-propylidine-5-O-tert-butyldimethylsilyl-α-d-xylofuranose-3-acrylate 3, with various aldehydes was conducted, resulting in adducts with moderate diastereoselectivity (5–40% e.e.).     

Rapid access to the synthesis of polysubstituted δ-lactones via tandem stereoselective conjugate addition/α-alkylation of unsaturated 7,3-lactone-α-d-xylofuranose derivative

α-d-xylo-7,3-Unsaturated lactone, a versatile chiral building block, undergoes Cu-catalyzed conjugated addition with high yield and stereoselectivity. When the conjugated reaction is quenched with a suitable alkyl halide, a tandem stereoselective conjugated/α-alkylation reaction is achieved. Further, selective hydrolysis of the 1,2-O-isopropylidene moiety followed by oxidative cleavage and reduction reaction, afforded the title compounds.     

Large scale synthesis of the acetonides of l-glucuronolactone and of l-glucose: easy access to l-sugar chirons

1,2-O-Isopropylidene-α-l-glucurono-3,6-lactone may be synthesized on a 100-200 g scale from cheaply available d-glucoheptonolactone in an overall yield of 94% in four steps via l-glucuronolactone. Subsequent elaboration to l-glucose, diacetone-l-glucose (1,2:5,6-di-O-isopropylidene-α-l-glucofuranose), and monoacetone-l-glucose (1,2-O-isopropylidene-α-l-glucofuranose) allows easy access to a range of l-sugar chirons.     

Metal-free,base catalyzed oxidative amination and denitration reaction: Regioselective synthesis of 3-arylimidazo[1,2-a]pyridines

A metal-free, regioselective strategy for the synthesis of 3-arylimidazo[1,2-a]pyridines from β-nitrostyrenes and 2-aminopyridines using triethylamine as the catalyst and H₂O₂ (30% aq.) as the oxidant is reported. The use of an inexpensive base and facile reaction conditions make this strategy a practical alternative for the synthesis of 3-arylimidazo[1,2-a]pyridines.     

Stereoselective synthesis of all stereoisomers of vicinal and distal bis(O-2-aminoethyl)-p-tert-butylthiacalix[4]arene

O,O″- and O,O′-bis(2-aminoethyl)-p-tert-butylthiacalix[4]arenes of anti conformation have been prepared by the reduction of the corresponding O,O″- and O,O′-bis(cyanomethyl) ethers. Their syn-O,O″- and O,O′-counterparts have been prepared by alternative routes via the Mitsunobu reaction of thiacalix[4]arene with N-(2-hydroxyethyl)phthalimide and the reduction of a O,O′-disiloxanediyl-bridged O″,O?-bis(cyanomethyl) ether of 1,2-alternate conformation, respectively. These products are expected to serve as useful precursors of highly elaborated synthetic receptors, including biscalixarenes.     

Grignard reagent-promoted 6-endo-dig cyclization: instantaneous synthesis of original dipyrido[1,2-a:3′,4′-d]imidazole

Dipyrido[1,2-a:3′,4′-d]imidazole derivatives can be readily synthetized from various 3-alkyne-2-cyanoimidazo[1,2-a]pyridines via an efficient Grignard reagent-promoted 6-endo-dig cyclization of nitrile to alkynes. A previous optimization of the Sonogashira coupling reaction at C(3) of the 2-cyanoimidazo[1,2-a]pyridine was necessary as this coupling reaction is known to be largely influenced by the nature of the 2-substituent.     

Rearrangement reactions in the fluorination of 3-deoxy-3-C-methyl-3-nitro-hexopyranosides (and hexo-1-thiopyranosides) of the d- and l-series by the DAST reagent

Fluorination of diverse 3-deoxy-3-C-methyl-3-nitro-hexopyranosides and hexo-1-thiopyranosides of the d- and l-series by the DAST reagent was studied in order to establish, on this 3-branched-chain sugar domain, the influence of the stereochemical relationship of the substituents at positions 1 and 2, as well as the protection of the HO-4, on the kinds of rearrangement reaction promoted by this fluorinating agent. Three classes of pyranosidic substrate were employed: (a) 1,2-trans configured, irrespective of whether HO-4 is protected or not; (b) 4-O-protected 1,2-cis configured; and (c) 4-O-unprotected 1,2-cis configured. They were prepared starting from simple glycosides through routes involving a Baer reaction and subsequent transformations by known methodology. All the substrates of class a essayed underwent, on treatment with DAST at room or higher temperatures, a rearrangement involving a 1,2-shift to give both the anomeric 2-inverted pyranosyl fluorides (or, for the 1-thioglycosides, only the α fluoride). Substrates of class b led, through a mechanism similar to that proposed for transformations of related substrates, to ring-contracted 2,5-anhydro-1-fluoro-1-O-methyl- (or 1-deoxy-1-phenylthio-)hexitol derivatives (sometimes as 1-epimers), which are precursors of 2,5-anhydro-aldehydo-sugars. Substrates of class c led to 4,5-anhydro-1-fluoro-1-O-methylalditol derivatives in all cases, together with a ring-contracted 5-fluoro-hexofuranoside in only one case; a rationalisation for their formation is proposed.     

Reactivity of sarcosine and 1,3-thiazolidine-4-carboxylic acid towards salicylaldehyde-derived alkynes and allenes

The reaction of sarcosine and 1,3-thiazolidine-4-carboxylic acid with salicylaldehyde-derived alkynes and allenes opened the way to new chromeno[4,3-b]pyrrole and chromeno[2,3-b]pyrrole derivatives. Tetrahydro-chromeno[4,3-b]pyrroles were obtained from the reaction of these secondary amino acids with O-propargylsalicylaldehyde. Interestingly, sarcosine reacted with ethyl 4-(2-formylphenoxy)but-2-ynoate to give a monocyclic pyrrole resulting from rearrangement of the initially formed 1,3-dipolar cycloadduct. Decarboxylative condensation of ethyl 4-(2-formylphenoxy)but-2-ynoate with 1,3-thiazolidine-4-carboxylic acid afforded in a stereoselective fashion the expected chromeno-pyrrolo[1,2-c]thiazole, which structure was unambiguously established by X-ray crystallography. However, the 1H,3H-pyrrolo[1,2-c]thiazole resulting from the opening of the pyran ring was also isolated. The reaction with O-buta-2,3-dienyl salicylaldehyde afforded 3-methylene-hexahydrochromeno[4,3-b]pyrrole. O-Allenyl salicylaldehyde reacted with sarcosine and 1,3-thiazolidine-4-carboxylic acid to give a new type of chromeno-pyrroles. A mechanism proposal for the synthesis of these chromeno[2,3-b]pyrroles has been presented.     

Synthesis and epimerization of 10-N-(6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-galactopyranos-6-yl)-(11aS)-pyrrolo[2,1-c][1,4]benzodiazepin-5,11-dione

The reaction of the 1,2:3,4-di-O-isopropylidene-6-O-tosyl-α-d-galactopyranose 2 with (11aS)-pyrrolo[2,1-c][1,4]benzodiazepin-5,11-dione 1, prepared from l-proline and isatoic anhydride, gave two products which were previously reported as conformational isomers. In this work, an X-ray crystallographic study showed these to be the diastereomeric pair (11aS)- and (11aR)-10-N-(6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-galactopyranos-6-yl)-pyrrolo[2,1-c][1,4]benzodiazepin-5,11-diones as a consequence of C(11a) epimerization in the benzodiazepine moiety during glycosylation under basic reaction conditions. The hydrosolubility of the deprotected products were compared with those of the analogous benzodiazepine derivatives.     

3-O-Acyl triggered tandem Lewis acid catalyzed intramolecular cyclization of diacetone glucose derivatives to 5-O-acyl-3,6-anhydro-d-glucose

BF₃ mediated one-pot conversion of 3-O-acyl-d-glucose-1,2:5,6-diacetonide derivatives to 5-O-acyl-3,6-anhydro-d-glucose is described through a tandem selective intramolecular cyclization sequence.     

A new, one-pot, three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines

A new, one-pot and three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines is described. The reactive 1:1 zwitterionic intermediate, formed by the addition of isocyanides to dialkyl acetylenedicarboxylates, was trapped by N-(2-heteroaryl)amides to yield a ketenimine intermediate, which was cyclized and then rearranged under the reaction conditions to afford the title compounds under mild reaction conditions in good yields. Single-crystal X-ray analysis conclusively confirms the structure of the obtained bridgehead bicyclic 6-6 heterocyclic compounds.     

One-pot synthesis of novel spiro 2,3,7,8-tetrahydro-benzo[1,2-b:5,4-b′]dipyran-4,6-dione and 2,3,8,9-tetrahydro-benzo[1,2-b:4,3-b′]dipyran-4,10-dione derivatives

An efficient synthesis of novel spiro 2,3,7,8-tetrahydro-benzo[1,2-b:5,4-b′]dipyran-4,6-dione and 2,3,8,9-tetrahydro-benzo[1,2-b:4,3-b′]dipyran-4,10-dione derivatives in high yields under microwave irradiation is described. The reaction was also studied under conventional heating conditions.     

Two new examples of the rare C→O migration of ethoxycarbonyl groups

Two new examples of a carbon→oxygen ethoxycarbonyl group shift are described. Treatment of 3-ethoxycarbonylnitromethyl-1,2-O-isopropylidene-6-O-p-toluenesulfonyl-α-d-allofuranose (4) with Bu₄NF leads to a rearrangement to 5-O-ethoxycarbonyl-1,2-O-isopropylidene-3-nitromethyl-6-O-p-toluenesulfonyl-α-d-allofuranose (8). Similar treatment of ethyl-3-O-benzyl-6-deoxy-6-nitro-d,l-glycero-d-glucoheptofuronate (12) gives 3-O-benzyl-4-O-ethoxycarbonyl-6-deoxy-6-nitro-d-glucopyranose (16).     

Synthesis of pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles by Curtius reaction in Morita-Baylis-Hillman derivatives

Synthesis of substituted pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles from the Morita-Baylis-Hillman derivatives of acrylates via saponification followed by Curtius reaction is described.