First Resolution of a Free Fluorophosphine Chiral at Phosphorus. Resolution and Reactions of Free and Coordinated (+/-)-Fluorophenylisopropylphosphine

The trivalent fluorophosphine (+/-)-PFPh(i-Pr), (+/-)-1, has been prepared by halogen exchange of the corresponding chlorophosphine with sodium fluoride in hot sulfolane. The neat fluorophosphine rapidly decomposes by equilibrium redox disproportionation into PF(3)Ph(i-Pr) and (R,R)/(R,S)-Ph(i-Pr)PPPh(i-Pr), but in benzene, (+/-)-1 has considerable thermodynamic stability. The resolution of (+/-)-1 was achieved by a fractional crystallization of the diastereomers (R,R(P))- and (R,S(P))-chloro[1-[1-(dimethylamino)ethyl]-2-naphthalenyl-C,N](fluorophenylisopropylphosphine)palladium(II), (R,R(P))- and (R,S(P))-5, whereby the less soluble (R,R(P)) diastereomer selectively crystallized in 64% yield in a typical second-order asymmetric transformation. Optically pure (S)-(-)-1, -210 (c 0.59, C(6)H(6)), was liberated from (R,R(P))-5 with (R,S)-1,2-phenylenebis(methylphenylphosphine). The optically active phosphine in benzene racemizes over 6 h without significant redox disproportionation. The methoxyphosphine (+/-)-P(OMe)Ph(i-Pr), (+/-)-9, was also resolved by the method of metal complexation. Thus, fractional crystallization of (R,R(P))- and (R,S(P))-chloro[1-[1-(dimethylamino)ethyl]-2-naphthalenyl-C,N](methoxyphenylisopropylphosphine)palladium(II), (R,R(P))- and (R,S(P))-8, followed by liberation of the respective optically active methoxyphosphines from the separated diastereomers with 1,2-bis(diphenylphosphino)ethane, gave (R)-(+)- and (S)-(-)-9 of 92% and 96% ee, respectively. The barrier to unimolecular inversion for (+/-)-9 was determined to be >82.9 +/- 0.5 kJ mol(-)(1) by variable temperature (1)H NMR spectroscopy. The substitution of fluoride in (R,R(P))-5 by methoxide proceeds with predominant inversion of the configuration at phosphorus to give (R,R(P))- and (R,S(P))-8 with (R,S(P))/(R,R(P)) = (1)/(5). The crystal structures of (R,R(P))-5 and (R,R(P))-8 have been determined: (R,R(P))-5 (C(23)H(28)ClFNPPd) crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 9.967(2) ?, b = 10.998(4) ?, c = 21.324(3) ?, Z = 4, and R = 0.031; (R,R(P))-8 (C(24)H(31)ClNOPPd) crystallizes in the space group P2(1)2(1)2(1) with a = 10.444(3) ?, b = 12.146(3) ?, c = 19.047(2) ?, Z = 4, and R = 0.026.     

Kinetics and mechanism of oxidation of N, N'-dimethylaminoiminomethanesulfinic acid by acidic bromate

The major metabolites of the physiologically active compound dimethylthiourea (DMTU), dimethylaminoiminomethansesulfinic acid (DMAIMSA), and dimethylaminoiminomethanesulfonic acid (DMAIMSOA) were synthesized, and their kinetics and mechanisms of oxidation by acidic bromate and aqueous bromine was determined. The oxidation of DMAIMSA is much more facile and rapid as compared to a comparable oxidation by the same reagents of the parent compound, DMTU. The stoichiometry of the bromate-DMAIMSA reaction was determined to be 2BrO 3 (-) + 3NHCH 3(NCH 3)CSO 2H + 3H 2O --> 3SO 4 (2) (-) + 2Br (-) + 3CO(NHCH 3) 2 + 6H (+), with quantitative formation of sulfate. In excess bromate conditions, the stoichiometry was 4BrO 3 (-) + 5NHCH 3(NCH 3)CSO 2H + 3H 2O --> 5SO 4 (2) (-) + 2Br 2 + 5CO(NHCH 3) 2 + 6H (+). The direct bromine-DMAIMSA reaction gave an expected stoichiometric ratio of 2:1 with no further oxidation of product dimethylurea (DMU) by aqueous bromine. The bromine-DMAIMSA reaction was so fast that it was close to diffusion-controlled. Excess bromate conditions delivered a clock reaction behavior with the formation of bromine after an initial quiescent period. DMAIMSOA, on the other hand, was extremely inert to further oxidation in the acidic conditions used for this study. Rate of consumption of DMAIMSA showed a sigmoidal autocatalytic decay. The postulated mechanism involves an initial autocatalytic build-up of bromide that fuels the formation of the reactive oxidizing species HBrO 2 and HOBr through standard oxybromine reactions. The long and weak C-S bond in DMAIMSA ensures that its oxidation goes directly to DMU and sulfate, bypassing inert DMAIMSOA.     

Trimethyl phosphite as a trap for alkoxy radicals formed from the ring opening of oxiranylcarbinyl radicals. Conversion to alkenes. Mechanistic applications to the study of C-C versus C-O ring cleavage

Trimethyl phosphite, (MeO)(3)P, is introduced as an efficient and selective trap in oxiranylcarbinyl radical (2) systems, formed from haloepoxides 8-13 under thermal AIBN/n-Bu(3)SnH conditions at about 80 degrees C. Initially, the transformations of 8-13, in the absence of phosphite, to allyl alcohol 7 and/or vinyl ether 5 were measured quantitatively (Table 1). Structural variations in the intermediate oxiranylcarbinyl (2), allyloxy (3), and vinyloxycarbinyl (4) radicals involve influences of the thermodynamics and kinetics of the C-O (2 --> 3, k(1)) and C-C (2 --> 4, k(2)) radical scission processes and readily account for the changes in the amounts of product vinyl ether (5) and allyl alcohol (7) formed. Added (MeO)(3)P is inert to vinyloxycarbinyl radical 4 and selectively and rapidly traps allyloxy radical 3, diverting it to trimethyl phosphate and allyl radical 6. Allyl radicals (6) dimerize or are trapped by n-Bu(3)SnH to give alkenes, formed from haloepoxides 8, 9, and 13 in 69-95% yields. Intermediate vinyloxycarbinyl radicals (4), in the presence or absence of (MeO)(3)P, are trapped by n-Bu(3)SnH to give vinyl ethers (5). The concentrations of (MeO)(3)P and n-Bu(3)SnH were varied independently, and the amounts of phosphate, vinyl ether (5), and/or alkene from haloepoxides 10, 11, and 13 were carefully monitored. The results reflect readily understood influences of changes in the structures of radicals 2-4, particularly as they influence the C-O (k(1)) and C-C (k(2)) cleavages of intermediate oxiranylcarbinyl radical 2 and their reverse (k(-1), k(-2)). Diversion by (MeO)(3)P of allyloxy radicals (3) from haloepoxides 11 and 12 fulfills a prior prediction that under conditions closer to kinetic control, products of C-O scission, not just those of C-C scission, may result. Thus, for oxiranylcarbinyl radicals from haloepoxides 11, 12, and 13, C-O scission (k(1), 2 --> 3) competes readily with C-C cleavage (k(2), 2 --> 4), even though C-C scission is favored thermodynamically.     

Synthesis of myo-inositol derivatives required for the total synthesis of surugatoxin, prosurugatoxin, and neosurugatoxin

Two myo-inositol derivatives (4) and (5), required for the total synthesis of surugatoxin, prosurugatoxin, and neosurugatoxin, were prepared. Synthesis of (+/-)-2,3-O-cyclohexylidene-4,5-O-isopropylidene-1-O-methoxymethyl-myo-i nositol (4) was achieved from (+/-)-1-O-benzoyl-2,3-O-cyclohexylidene-4,5-O-isopropylidene-myo-inosito l (6) in 4 steps, and (-)-2,3-O-cyclohexylidene-1,4-di-O-methoxymethyl-5-O-[2',3',4'-tri-O-ace tyl- beta-D-xylopyranosyl]-myo-inositol (5) was synthesized from (+/-)-1-O-benzoyl-2,3-O-cyclohexylidene-5,6-O-isopropylidene-myo-inosito l (12) in 7 steps.     

Reactivity of cyclooligophosphanes: synthesis and structural characterisation of cyclo-1,4-(BH3)2(P4Ph4CH2) and cyclo-1,2-(BH3)2(P5Ph5)

The borane complexes cyclo-1,4-(BH3)2(P4Ph4CH2) (3) and cyclo-1,2-(BH3)2(P5Ph5) (4) were prepared by reaction of cyclo-(P4Ph4CH2) and cyclo-(P5Ph5) with BH3(SMe2). Only the 2:1 complexes 3 and 4 were isolated, even when an excess of the borane source was used. In solution, 3 exists as a mixture of the two diastereomers (R(P)*,S(P)*,S(P)*,R(P)*)-(+/-)-3 and (R(P)*,R(P)*,R(P)*,R(P)*)-(+/-)-3. However, in the solid state the (R(P)*,S(P)*,S(P)*,R(P)*)-(+/-) diastereomer is the major stereoisomer. Similarly, while only one isomer of 4 is observed in its X-ray structure, NMR spectroscopic investigations reveal that it forms a complex mixture of isomers in solution. 3 may be deprotonated with tBuLi to give the lithium salt cyclo-1,4-(BH3)2(P4Ph4CHLi) (3 x Li), though this could not be isolated in pure form.     

Scope and limitations of the double [4+3]-cycloadditions of 2-oxyallyl cations to 2,2'-methylenedifuran and derivatives

The reactivity of various 2-oxyallyl cations toward 2,2'-methylenedifuran (1b), 2,2'-(hydroxymethyl)difuran (1c), 2,2'-(trimethylsilylmethylene)difuran (1d), and di(2-furyl)methanone (1e) has been explored. Difuryl derivatives 1c, 1d, and 1e refused to undergo formal double [4+3]-cycloadditions. Conditions have been found to convert 1b into meso-1,1'-methylenedi[(1R,1'S,5S,5'R)- (3) and (+/-)-1,1'-methylenedi[(1RS,1'SR,5SR,5'RS)-8-oxabicyclo[3.2.1]oct-6-en-3-one] (4) that do not require CF(3)CH(OH)CF(3) as solvent. High yields of meso-1,1'-methylenedi[(1R,1'S,2S,2'R,4R,4'S,5S,5'R)- (5) and (+/-)-1,1'-methylenedi[(1RS,1'RS,2SR,2'SR,4RS,4'RS,5SR,5'SR)-2,4-dimethyl-8-oxabicyclo[3.2.1]oct-6-en-3-one] (6) have been obtained when 1b was reacted with 2,4-dibromopentan-3-one (7h) and NaI/Cu.     

Highly efficient total synthesis of the marine natural products (+)-avarone, (+)-avarol, (-)-neoavarone, (-)-neoavarol and (+)-aureol

Biologically important and structurally unique marine natural products avarone (1), avarol (2), neoavarone (3), neoavarol (4) and aureol (5), were efficiently synthesized in a unified manner starting from (+)-5-methyl-Wieland-Miescher ketone 10. The synthesis involved the following crucial steps: i) Sequential BF(3)Et(2)O-induced rearrangement/cyclization reaction of 2 and 4 to produce 5 with complete stereoselectivity in high yield (2 --> 5 and 4 --> 5); ii) strategic salcomine oxidation of the phenolic compounds 6 and 8 to derive the corresponding quinones 1 and 3 (6 --> 1 and 8 --> 3); and iii) Birch reductive alkylation of 10 with bromide 11 to construct the requisite carbon framework 12 (10 + 11 --> 12). An in vitro cytotoxicity assay of compounds 1-5 against human histiocytic lymphoma cells U937 determined the order of cytotoxic potency (3 > 1 > 5 > 2 > 4) and some novel aspects of structure-activity relationships.     

Pregnane- and furostane-type oligoglycosides from the seeds of Allium tuberosum

Two furostane-type steroidal oligoglycosides (1, 2), together with a new pregnane-type oligoglycoside (3), were obtained from the seeds of Allium tuberosum ROTTLER. On the basis of spectroscopic analysis, the structures of three new oligoglycosides (1-3) were elucidated as 26-O-beta-D-glucopyranosyl-(25R)-3beta,22xi,26-trihydroxyl-5alpha-furostane 3-O-beta-chacotrioside, 26-O-beta-D-glucopyranosyl-(25S)-3beta,5beta,6alpha,22xi,26-pentahydroxyl-5beta-furostane 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranoside, and 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl 3beta,5beta,6alpha,16beta-tetrahydroxypregnane 16-(5-O-beta-D-glucopyranoyl-4(S)-methyl-5-hydroxypentanoic acid) ester, respectively.     

Steroidal oligoglycosides from the seeds of Allium tuberosum

Three new spirostanol steroidal oligoglycosides, together with a known oligoglycoside, were obtained from the seeds of Allium tuberosum after enzymatic hydrolysis of furostanol saponin fraction by beta-glucosidase. On the basis of spectroscopic analysis, the structure of new spirostanol oligoglycosides were elucidated as (25S)-spirost-5-ene-2alpha,3beta-diol 3-O-alpha-L-rhamnopyranosyl-(1-->4)-[alpha-L-rhamnopyranosyl-(1-->2)]-be ta-D-glucopyranoside, (25S)-spirostane-3beta,5beta,6alpha-triol 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranoside, and (25S)-5beta-spirostane-3beta,6alpha-diol 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranoside.     

Syntheses of 2-chloro-4-nitrophenyl beta-D-maltopentaosides with bulky modification and their application to the differential assay of human alpha-amylases.

Four novel maltopentaosides, 2-chloro-4-nitrophenyl O-(6-O-p-toluenesulfonyl-alpha-D-glucopyranosyl)-(1-->4)-tris[O- alpha-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (4), 2-chloro-4-nitrophenyl O-[6-O-(tert-butyldimethyl)silyl-alpha-D- glucopyranosyl]-(1-->4)-tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D- glucopyranoside (5), 2-chloro-4-nitrophenyl O-[6-deoxy-6-(phenyl)sulfonyl-alpha-D- glucopyranosyl]-(1-->4)-tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D- glucopyranoside (10), and 2-chloro-4-nitrophenyl O-(6-deoxy-6-phthalimido-alpha-D-glucopyranosyl)- (1-->4)-tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (11) were synthesized. Substrates 4, 5, 10, and 11 were hydrolyzed by human pancreatic alpha-amylase (HPA) from 1.1 to 2.9-fold faster than by human salivary alpha-amylase (HSA). Taking advantage of the difference in the hydrolytic rate of 5 (2.9-fold faster), we developed a new method for the differential assay of these two human alpha-amylases.     

Thermodynamics of the molecular and chiral recognition of cycloalkanols and camphor by modified beta-cyclodextrins possessing simple aromatic tethers

The complex stability constants (K(S)) and thermodynamic parameters (DeltaG degrees, DeltaH degrees, and TDeltaS degrees ) for 1:1 inclusion complexation of beta-cyclodextrin (beta-CD) derivatives, 6-O-phenyl-beta-CD (2) 6-O-(4-formyl-phenyl)-beta-CD (3), 6-O-(4-nitrophenyl)-beta-CD (4), 6-O-(4-bromophenyl)-beta-CD (5), 6-O-(4-chlorophenyl)]-beta-CD (6), and 6-O-(4-hydroxybenzoyl)-beta-CD (7) with representative guest molecules, cyclic alcohols (cyclopentanol, cyclohexanol, cycloheptanol, cyclooctanol), (+/-)-borneol, and (+/-)-camphor, have been determined by means of titration microcalorimetry in an aqueous phosphate buffer solution (pH = 7.20) at 298.15 K. The results obtained indicate that the introduction to beta-CD of an aromatic ring bearing different substituent groups significantly enhances the molecular binding ability and moderately alters the chiral discrimination ability for the guests examined here, displaying the highest enantioselectivity of up to 4.01 for the inclusion complexation of 6 with (+/-)-camphor. The enhanced molecular/chiral discrimination ability caused by derivatization is attributed solely to increased positive entropy changes due to the expanding hydrophobic interaction and desolvation effects. The binding modes of host-guest interactions derived from ROESY spectroscopy data show that the resulting complex of 4 and (+)-borneol possesses better induced-fit interaction as compared to (-)-borneol, which is responsible for the enhanced molecular/chiral recognition ability.     

Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities

Five new withanolide derivatives (1, 9-12) were isolated from the roots of Withania somnifera together with fourteen known compounds (2-8, 13-19). On the basis of spectroscopic and physiochemical evidence, compounds 1 and 9-12 were determined to be (20S,22R)-3 alpha,6 alpha-epoxy-4 beta,5 beta,27-trihydroxy-1-oxowitha-24-enolide (1), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside VIII, 9), 27-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside IX, 10), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranoside (withanoside X, 11), and (20R,22R)-1 alpha,3 beta,20,27-tetrahydroxywitha-5,24-dienolide 3-O-beta-D-glucopyranoside (withanoside XI, 12). Of the isolated compounds, 1, withanolide A (2), (20S,22R)-4 beta,5 beta,6 alpha,27-tetrahydroxy-1-oxowitha-2,24-dienolide (6), withanoside IV (14), withanoside VI (15) and coagulin Q (16) showed significant neurite outgrowth activity at a concentration of 1 microM on a human neuroblastoma SH-SY5Y cell line.     

Total syntheses of five indole alkaloids from the marine bryozoan Flustra foliacea

A general, efficient, and conceptually new approach to the total syntheses of marine-derived indole alkaloids, including (+/-)-flustramines A (1) and B (2), (+/-)-flustramides A (3) and B (4), and (+/-)-debromoflustramine B (5), is outlined. The key step in the syntheses involves the conjugated addition of an organomagnesium species derived from prenyl bromide to 2-hydroxyindolenines. Compounds 1, 2, and 5 have been synthesized in five steps with 23%, 17%, and 16% overall yield, respectively, whereas flustramides 3 and 4 have been synthesized in only four steps with 24% and 18% overall yield, respectively, on the basis of 2-hydroxyindolenines.     

Synthesis and resolution of (R,R)-(+/-)-1,1,4,7,10,10-hexaphenyl-1,10-diarsa-4,7-diphosphadecane: new ligand for the stereoselective self-assembly of dicopper(I), disilver(I), and digold(I) helicates

Diphenylvinylarsine oxide reacts with 1,2-bis(phenylphosphino)ethane in the presence of potassium tert-butoxide to give the anti-Markovnikov product (R,R)-(+/-)/(R,S)-1,1,4,7,10,10-hexaphenyl-1,10-diarsa-4,7-diphosphadecane dioxide-1AsO,10AsO, which, upon reduction with HSiCl(3)/NEt(3) in boiling acetonitrile, affords in 84% overall yield the di(tertiary arsine)-di(tertiary phosphine) (R,R)-(+/-)/(R,S)-diphars. After separation of the diastereomers by fractional crystallization, the (R,R)-(+/-) form of the ligand was resolved by metal complexation with (+)-di(mu-chloro)bis[(R)-1-[1-(dimethylamino)ethyl]-2-phenyl-C(2),N]dipalladium(II): (R,R)-diphars, mp 87-88 degrees C, has [alpha](D)(21) = -18.6 (c 1.0, CH(2)Cl(2)); (S,S)-diphars has [alpha](D)(21) = +18.4 (c 1.0, CH(2)Cl(2)). The crystal and molecular structures of the complexes (M)-[M(2)[(R,R)-diphars](2)](PF(6))(2) (M = Cu, Ag, Au) have been determined: [M-(S(Cu),S(Cu))]-(-)-[Cu(2)[(R,R)-diphars](2)](PF(6))(2), orthorhombic, P2(1)2(1)2(1) (No. 19), a = 16.084(3) A, b = 18.376(3) A, c = 29.149(6) A, Z = 4; [M-(S(Ag),S(Ag))]-(+)-[Ag(2)[(R,R)-diphars](2)](PF(6))(2), triclinic, P1, a = 12.487(2) A, b = 12.695(4) A, c = 27.243(4) A, alpha = 92.06 degrees, beta = 95.19 degrees, gamma = 98.23 degrees, Z = 2; [M-(S(Au),S(Au))]-(-)-[Au(2)[(R,R)-diphars](2)](PF(6))(2), orthorhombic, P2(1)2(1)2(1) (No. 19), a = 16.199(4) A, b = 18.373(4) A, c = 29.347(2) A, Z = 4. In the copper(I) and gold(I) helicates, each ligand strand completes 1.5 turns of an M helix in a parallel arrangement about the two chiral MAs(2)P(2) stereocenters of S configuration. The unit cell of the silver(I) complex contains one molecule each of the parallel helicate of M configuration and the conformationally related double alpha-helix of M configuration in which each ligand strand completes 0.5 turns of an M helix about two metal stereocenters of S configuration. Energy minimization calculations of the three structures with use of the program SPARTAN 5.0 gave results that were in close agreement with the core structures observed.     

Five new phenylethanoid glycosides from the whole plants of Lamium purpureum L

Five new phenylethanoid glycosides, lamiusides A (1), B (2), C (3), D (4) and E (5), were isolated from the whole plants of Lamium purpureum L. (Labiatae) together with seven known compounds (6-12). On the basis of chemical and spectral analyses, the structures of the new compounds were elucidated to be 2-(3,4-dihydroxyphenyl)ethyl-O-beta-D-galactopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)-(4-O-trans-caffeoyl)-beta-D-glucopyranoside (1), 2-(3,4-dihydroxyphenyl)ethyl-O-beta-D-galactopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)-(4-O-trans-feruloyl)-beta-D-glucopyranoside (2), 2-(3,4-dihydroxyphenyl)ethyl-O-beta-D-galactopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)-(6-O-trans-caffeoyl)-beta-D-glucopyranoside (3), 2-(3,4-dihydroxyphenyl)-R,S-methoxy-ethyl-O-beta-D-galactopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)-(4-O-trans-caffeoyl)-beta-D-glucopyranoside (4) and 2-(3-hydroxy-4-methoxyphenyl)ethyl-O-alpha-L-rhamnopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->6)-(4-O-cis-feruloyl)-beta-D-glucopyranoside (5). In addition, the radical-scavenging activities of compounds 1-4 on 1,1-diphenyl-2-picrylhydrazyl radical were examined.     

Solid-phase synthesis of O-sulfated glycopeptide by the benzyl-protected glycan strategy

To expand the repertoire of our benzyl-protection strategy for solid-phase glycopeptide synthesis, an O-sulfated glycopeptide was chosen as the synthetic target. Trisaccharyl serine derivatives (Galβ1-4-GlcNAcβ1-2-Manα1-3-Ser) carrying (4-methoxyphenyl)methyl (MPM) groups at either 3-O or 6-O of the Gal residue were prepared through three stereoselective glycosylations. Cleavage of MPM followed by reaction with Me₃N·SO₃ efficiently afforded 3-O- and 6-O-sulfo-glycoserines, respectively. A preliminary debenzylation study using the sulfated glycoserines revealed that the sulfate groups persisted under ‘low-acidity TfOH’ conditions, when using a limited amount of TfOH and extending the reaction period. The 3-O-sulfo-glycoserine was then introduced into an icosapeptide modeled after an α-dystroglycan fragment by a combination of automated and manual solid-phase peptide synthesis procedures. The synthesized glycopeptide was successfully debenzylated by the low-acidity TfOH cocktail with slight damage to the sulfate functionality.     

Chemoenzymatic synthesis of phosphocarnitine enantiomers

Racemic phosphocarnitine 3 has been synthesized starting from diethyl 3-chloro-2-oxopropanephosphonate 4 in three steps involving reduction of 4 to the corresponding 2-hydroxyphosphonate 5, conversion of the latter to phosphonic acid 6, and final reaction with trimethylamine, affording the trimethylammonium salt of 3. Baker's yeast reduction of 4 and enzymatic kinetic resolution of (+/-)-5 afforded the enantiomerically pure precursors of phosphocarnitine, (R)-(+)-5 and (S)-(-)-5, which were converted to (S)-(-)- and (R)-(+)-phosphocarnitine 3, respectively.     

Molecular design of luminescence ion probes for various cations based on weak gold(I)...gold(I) interactions in dinuclear gold(I) complexes

A series of luminescent dinuclear gold(I) complexes with different crown ether pendants, [Au(2)(PwedgeP)(S-B15C5)(2)] [S-B15C5 = 4'-mercaptobenzo-15-crown-5, P(wedge)P = bis(dicyclohexylphosphino)methane (dcpm) (1), bis(diphenylphosphino)methane (dppm) (2)] and [Au(2)(P(wedge)P)(S-B18C6)(2)] [S-B18C6 = 4'-mercaptobenzo-18-crown-6, P(wedge)P = dcpm (3), dppm (4)], and their related crown-free complexes, [Au(2)(P(wedge)P)(SC(6)H(3)(OMe)(2)-3,4)(2)] [P(wedge)P = dcpm (5), dppm (6)], were synthesized. The low-energy emission of the mercaptocrown ether-containing gold(I) complexes are tentatively assigned as originated from states derived from a S --> Au ligand-to-metal charge transfer (LMCT) transition. The crown ether-containing gold(I) complexes showed specific binding abilities toward various metal cations according to the ring size of the crown pendants. Spectroscopic evidence was provided for the metal-ion-induced switching on of the gold...gold interactions upon the binding of particular metal ions in a sandwich binding mode.     

Total synthesis of (+/-)-flustramines A and C, (+/-)-flustramide A, and (-)- and (+)-debromoflustramines A

Here we describe the efficient total synthesis of the three title hexahydropyrrolo[2,3-b]indole alkaloids and debromo derivative from readily available indolin-3-ones using key domino reactions, olefination-isomerization-Claisen rearrangement (OIC), and reductive cyclization (RC). (+/-)-Flustramine C (5) was synthesized in five steps from 6-bromoindolin-3-one 9 via a key intermediate 13a. (+/-)-Flustramine A (1) has been obtained by reduction of flustramide A (6), which has been prepared in five steps from 13a. (+/-)-Debromoflustramine A (19) was provided in a similar manner from 13b. The (-)- and (+)-enantiomers of 19 were synthesized through optical resolution of (+/-)-carboxylic acid 17b using (R)-4-phenyloxazolidin-2-one.     

Synthesis and conjugation of oligosaccharide analogues of fragments of the immunoreactive glycan part of the circulating anodic antigen of the parasite Schistosoma mansoni

The gut-associated circulating anodic antigen (CAA) is one of the major excretory antigens produced by the parasite Schistosoma mansoni. The immunoreactive part of CAA is a threonine-linked polysaccharide composed of long stretches of the unique repeating disaccharide-->6)-[beta-D-GlcpA-(1-->3)]-beta-D-GalpNAc-(1-->. Previously, using surface plasmon resonance and ELISA techniques, it has been shown that some anti-CAA IgM monoclonal antibodies (MAbs) also recognize members of a series of bovine serum albumin (BSA)-coupled synthetic di- to penta-saccharide fragments of the CAA glycan. To generate information on the molecular level about the glycan specificity of the relevant IgM MAbs, two series of oligosaccharides related to the CAA disaccharide epitope were synthesized, and coupled to BSA. The first three analogues, beta-D-GlcpA-(1-->3)-[small beta]-D-GlcpNAc-(1-->O), beta-D-GlcpNAc-(1-->6)-[beta-D-GlcpA-(1-->3)]-beta-D-GlcpNAc-(1-->O), and beta-D-GlcpA-(1-->3)-beta-D-GlcpNAc-(1-->6)-[beta-D-GlcpA-(1-->3)]-beta-D-GlcpNAc-(1-->O), wherein the native beta-D-GalpNAc moiety was replaced by beta-D-GlcpNAc, were synthesized to investigate the specificity of the selected MAbs to the carbohydrate backbone of CAA. The second series of analogues, beta-D-Glcp6S-(1-->3)-beta-D-GalpNAc-(1-->O), beta-D-GalpNAc-(1-->6)-[beta-D-Glcp6S-(1-->3)]-beta-D-GalpNAc-(1-->O), and beta-D-Glcp6S-(1-->3)-beta-D-GalpNAc-(1-->6)-[beta-D-Glcp6S-(1-->3)]-beta-D-GalpNAc-(1-->O), wherein the native beta-D-GlcpA moiety was replaced by beta-D-Glcp6S, was synthesized to evaluate the importance of the type/nature of the charge of CAA for the MAb recognition.