Branched-chain Cyclitols Research Articles

ChemInform Abstract: Synthesis of Branched Chain Cyclitols: Preparation of Some Useful Chiral Building Blocks.

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Free-radical mediated synthesis of enantiomerically pure, highly functionalized inositols from carbohydrates

We report the synthesis, free-radical cyclization of precursors 1,2,7-trideoxy-7-iodo-3,4:5,6-di- O-isopropylidene- d- gluco-hept-1-enitol ( 1), methyl 7- O-acetyl-6- O-benzyl-8-bromo-2,3,8-trideoxy-4,5- O-isopropylidene- d- gluco-oct-2-enonate ( 2) and 5- O-acetyl-4- O-benzyl-6-bromo-6-deoxy-2,3- O-isopropylidene- d-glucose- O-benzyloxime ( 3), readily prepared from d-glucose, and some selected transformations of the carbocycles obtained from these intermediates. In compound 1 we have installed a terminal double bond and an iodide as radical acceptor and leaving group, respectively. Compounds 2 and 3 are ε-bromo aldehydes substituted with α,β-unsaturated ester and oxime ether functions as radical traps, respectively. The tributyltin hydride mediated ring closure of these radical precursors have afforded a series of interesting, diverse and highly functionalized carbocycles which can be considered useful building blocks for the synthesis of branched-chain cyclitols, aminocyclitols and aminoconduritols. In these processes, a good chemical yield and high stereoselectivity has been found in the newly formed stereocenters. Particularly interesting has been the finding that the stereochemical outcome of the free-radical cyclization is independent of the ratio of isomers ( E or Z) in oxime ether 3. These results show the power and the state of art of this strategy for the stereocontrolled synthesis of enantiomerically pure inositols from carbohydrates.

Synthesis of new anhydro and branched-chain cyclitols

Starting from d-glucose and d-(−)-quinic acid (5) (1 S,5 R,6 S)-5-azido-6-benzyloxycyclohex-2-en-1-ol (3), and the structurally related α,β-unsaturated alcohols 7 and 8, respectively, were prepared. They have been transformed, by treatment with 3-chloroperoxybenzoic acid, into (1 R,2 S,3 R,5 S,6 R)-3-azido-2-benzyloxy-5,6-epoxycyclohexane-1-ol (4) and the two diastereoisomeric 4,5-isopropylidenedioxycyclohexane-1-ols 9 and 10. Thermal Claisen rearrangement of the allylic alkcohols 3, 7 and 8 resulted in the functionalized branched-chain cyclohexenyl acetamides 12, 13 and 14, respectively. The prepared new cyclitols are useful starting materials for further derivatization to obtain novel enzyme-inhibitors, including phosphorylated cyclitols with “second-messenger” properties.

Stereoelectronic effects in the 6-exo free radical cyclization of acyclic sugar derivatives: synthesis of branched chain cyclitols

The synthesis and free radical carbocyclization (Bu 3 SnH+AIBN) of acyclic sugar derivatives 1-12 is reported. The yields of these 6-exo cyclization processes are good and the diastereomeric excesses are from moderate to excellent. The resulting cyclohexanes are polyoxygenated, enantiomerically pure building blocks for the synthesis of complex branched chain cyclitols. The results obtained in the cyclization of radical precursors 1, 4, 6, and 8 are in sharp contrast with the results observed in the ring closure of compounds 2, 3, 5, and 7. An electron-attracting group (acetate or mesylate), located in a vicinal position to the carbon-centered radical, modifies the conformation of the reacting species in the transition state and thus changes the stereochemical outcome of the cyclisation

Synthesis of branched-chainD-myo-inositols using the [3,3]sigmatropic Claisen rearrangement

A new and efficient synthesis of branched-chain cyclitols and their congeners utilizing a stereospecific Claisen rearrangement is reported.

Branched Chain Cyclitols: Asymmetric Synthesis Of A 1α, 25-Dihydroxy-19-Nor-Vitamin D3A-Ring Synthon

Abstract The 6-Exo Free Radical Cyclization Of The Carbohydrate Derivative 5 Gives In High Yield And Moderate Diastereomeric Excess The Carbocycle 4 Which Has Been Transformed Into A 1α, 25-Dihydroxy-19-Nor-Vitamin D3 A-Ring Synthon.

Synthesis of branched chain cyclitols: preparation of some useful chiral building blocks

The conveniently functionalized carbohydrate intermediates 1-4 and 9 undergo 6-exo free radical intramolecular cyclization giving branched chain cyclitols in good yield and low to good diastereoselectivity. These compounds are useful chiral building blocks for further manipulation.

Synthesis of branched-chain cyclitols using a palladium(0)-catalysed allylic coupling reaction

A carbanion derived from Meldrum's acid was used in α palladium(0)-catalysed allylic substitution reaction to prepare stereospecifically branched-chain cyclitols from the symmetrical 1,2,3,4-tetraacetoxyclyclohex-5-ene ( 4).

Synthetic ventures in pseudo-sugar chemistry

Pseudo-sugar is a compound in which a ring-oxygen of a pyranoid sugar is replaced by a methylene group, and there are 32 theoretically possible stereoisomers in the pseudo-sugar family. All the predicted 16 DL-forms have been synthesized, as well as 9 enantiomers. The most accessible starting material for a synthesis of pseudo-sugars is endo-7-oxabicyclo[2.2.l]hept-5-ene-2-carboxylic acid which is obtained by the DielsAlder reaction of furan and acrylic acid. Recently, it has been found that some pseudo-sugars are almost equally sweet as their respective true sugars. INTRODUCTION In the last two decades, several biologically active branched-chain cyclitols and their erivatives have been found in Nature, such as (+)-(l,2,3/4,5)-tetrahydroxy-l-cyclohexanemethanol (1) (ref. 1), validamycin antibiotics (2) (ref. 2), glucosidase-inhibitors: acarbose (ref. 3), trestatins (ref. 4), adiposins (ref. 5) and oligostatins (refs. 6, 7). Since their common component, hydroxymethyl-cyclohexanetetrol or its amino derivative, is structurally closely related to a true sugar, this compound has been designated as a pseudosugar or a pseudo-amino sugar. Thus, the pseudo-sugar is a name of a class of compounds in which a ring-oxygen of a pyranoid sugar is replaced by a methylene group.

Total synthesis of (+)-(1,2,3/4,5)-2,3,4,5-tetrahydroxycyclohexane-1-methanol and (+)-(1,3/2,4,5)-5-amino-2,3,4-trihydroxycyclohexane-1-methanol [(+)-validamine]. X-Ray crystal structure of (3S)-(+)-2-exo-bromo-4,8-dioxatricyclo[4.2.1.O]nonan-5-one

The optical resolution of (±)-7-endo-oxabicyclo[2.2.1]hept-5-ene-2-carboxylic acid (±)-(1) has been accomplished by use of (R)-(+)- and (S)-(–)-α-methylbenzylamine, respectively. The absolute configuration of (–)-(1) has been determined on the basis of X-ray analysis of the bromo lactone (2) derived from it. The title branched-chain cyclitol (6), the antibiotic produced by Streptomyces sp. MA-4145, has been totally synthesized from (–)-(1), its absolute configuration being established. Synthesis of the penta-N,O-acetyl derivative (12) of (+)-validamine, the branched-chain aminocyclitol obtained by degradation of the antibiotic validamycin A, has also been carried out from (–)-(1).

ChemInform Abstract: TOTAL SYNTHESIS AND ABSOLUTE CONFIGURATION OF (+)‐(1,2,3/4,5)‐2,3,4,5‐TETRAHYDROXY‐1‐CYCLOHEXANEMETHANOL

AbstractRacemische endo‐Oxabicyclo[2.2.l lheptencarbonsäure wird mit R‐(+)‐a‐Methylbenzylamin in die Enantiomeren getrennt.

TOTAL SYNTHESIS AND ABSOLUTE CONFIGURATION OF (+)-(1,2,3/4,5)-2,3,4,5-TETRAHYDROXY-1-CYCLOHEXANEMETHANOL

Abstract The title branched-chain cyclitol has been synthesized from chiral 7 endo-oxabicyclo[2.2.1]hept-5-ene-2-carboxylic acid, the absolute configuration of which was established on the basis of X-ray analysis of crystalline bromolactone derived from it. From this result the C-1 configuration of the cyclitol is determined to be R.

ChemInform Abstract: SYNTHETIC STUDIES ON THE VALIDAMYCINS. IX. SYNTHESIS OF SOME RACEMIC ISOMERS OF VALIDOXYLAMINE A

Two racemic isomers of validoxylamine A have been synthesized by use of coupling reactions of the protected DL-validamine and the allylbromides, the precursors of the unsaturated branched-chain cyclitol moiety. The racemic diastereomers thus formed can be separated by chromatography on silica gel. It indicates that optically pure validoxylamine A analogs should be obtained if chiral validamine derivative is used in place of the racemate.

Synthetic Studies on the Validamycins. IX. Synthesis of Some Racemic Isomers of Validoxylamine A

Abstract Two racemic isomers of validoxylamine A have been synthesized by use of coupling reactions of the protected Dl-validamine and the allylbromides, the precursors of the unsaturated branched-chain cyclitol moiety. The racemic diastereomers thus formed can be separated by chromatography on silica gel. It indicates that optically pure validoxylamine A analogs should be obtained if chiral validamine derivative is used in place of the racemate.

A TOTAL SYNTHESIS OF 6″-EPIVALIDAMYCIN A AND ITS DIASTEREOMER

Abstract A total synthesis of the 6″-epimer of validamycin A and its diastereomer has been accomplished by a coupling reaction of the racemic peracyl 5,6-dihydroxy-1-hydroxymethyl-1,3-cyclohexadiene monoepoxide, the precursor of the unsaturated branched-chain cyclitol portion, with the protected β-d-glucopyranosylvalidamine, followed by acid hydrolysis and O-deacylation.

ChemInform Abstract: SYNTHESIS OF SOME RACEMIC ISOMERS OF VALIDOXYLAMINE A

AbstractAus dem Cyclohexylbromid (I) erhält man über 5 Stufen das Amin (II), das mit dem Bromid (III) zu den diastereomeren Aminen (IV) und (V) und mit dem Bromid (VI) zu den Validoxylamin‐A‐Isomeren (VIIc) und (VIIIc) umgesetzt wird.

SYNTHESIS OF SOME RACEMIC ISOMERS OF VALIDOXYLAMINE A

Abstract Two racemic isomers of validoxylamine A were synthesized by the condensation reaction of the blocked Dl-validamine and the allyl bromide, the precursor of the unsaturated branched-chain cyclitol moiety.

Branched-chain Sugars. XXI. Synthesis of New Branched-chain Cyclitols Having neo-, myo-, and chiro-Configurations from 3-O-Benzyl-5,6-dideoxy-5-C-(1,3-dithian-2-yl)-6-nitro-d-galactofuranose and -l-altrofuranose

Abstract The Michael addition of 2-lithio-1,3-dithiane to 3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-6-nitro-β-l-arabino-hex-5-enofuranose afforded a 1 : 1.8 mixture of 3-O-benzyl-5,6-dideoxy-5-C-(1,3-dithian-2-yl)-1,2-O-isopropylidene-6-nitro-α-d-galactofuranose and-β-l-altrofuranose. Removal of the isopropylidene group and intra-molecular cyclization under weakly basic conditions afforded a mixture of branched-chain cyclitols having neo-, myo-, and chiro-configuration. A similar cyclization of the O-deisopropylidenated product of 3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-6-nitro-5-C-(nitromethyl)-β-l-arabino-hexofuranose also afforded a mixture of cyclitols having neo-, myo-, and chiro-configuration. The results confirm the importance of two bulky groups such as benzyloxy at C-3 and 1,3-dithiane residue at C-5 in determining the stereodirection of cyclization.

ChemInform Abstract: SYNTHESIS OF PENTA‐N,O‐ACETYL‐DL‐VALIENAMINE AND ITS RELATED BRANCHED‐CHAIN UNSATURATED AMINOCYCLITOLS AND CYCLITOLS

AbstractDas Cyclohexentriol‐trisacetat (I) wird bromiert, die dabei gebildeten isomeren Dibromide (II) werden getrennt und daraus die Derivate (III) hergestellt.

Branched-chain halo- and animo-cyclitols: synthesis and an x-ray crystallographic study

The base-catalyzed cyclizations of tri- O-acetyl-1,7-dibromo-1,7-dideoxy- xylo-2,6-heptodiulose ( 2), tri- O-acetyl-1,7-dichloro-1,7-dideoxy- xylo-2,6-heptodiulose ( 3), and tri- O-acetyl-1,7-di- C-azido-1,7-dideoxy- xylo-2,6-heptodiulose ( 4), to dL-4,5,6-tri- O-acetyl-2- C-bromo-3-C-(bromomethyl)- 2, 3, 4, 6/ 5-tetrahydroxycyclohexanone ( 5), dL-4,5,6-tri- O-acetyl-2-chloro-3- C-(chloromethyl)- 2, 3, 4, 6/ 5-tetrahydroxycyclohexanone ( 6), and dL-4,5,6-tri- O-acetyl-2- C-azido-3- C-(azidomethyl)- 2, 3, 4, 6/ 5-tetrahydroxycyclohexanone ( 7), respectively, are described. Reduction of the acetylated cycloses 5–7 by sodium borohydride proceeded with considerable stereoselectivity in producing branched epi-inositols, isolated as the tetraacetates 12, 13, and 18. These latter compounds were used to prepare the corresponding unprotected cyclitols 24, 25, and 31, and the branched amino- epi-inositols 27, 29, 30, and 32. The stereochemistry of the branched-chain cyclitols described appears to be the same as that of dL-1,4,5,6-tetra- O-acetyl-3-chloro-2- C-(chloromethyl)- epi-inositol ( 13), whose structure was confirmed by an X-ray crystallographic study.