Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with size-exclusion chromatographic fractionation for structural characterization of synthetic aliphatic copolyesters

We report matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and off-line coupling of size-exclusion chromatography with MALDI-TOFMS analysis (SEC/MALDI-TOFMS) methods for the detailed characterization of poly[(R,S)-3-hydroxybutyrate-co-L-lactic acid], P[(R,S)-3HB-co-LA], and poly[(R,S)-3-hydroxybutyrate-co-epsilon-caprolactone], P[(R,S)-3HB-co-CL], copolymer samples which are expected to be used in special medical application as scaffolds for cartilage and soft tissue engineering. The novel copolyesters contained randomly distributed (R,S)-3-hydroxybutyrate structural units, were synthesized by transesterification of the corresponding homopolymers, i.e. atactic poly[(R,S)-3-hydroxybutyrate], a-PHB, and poly(L-Lactide) (PLLA) or poly(epsilon-caprolactone) (PCL), respectively. The MS methods used for the characterization of the resulting polydisperse copolyester samples were supported by classical methods (NMR, SEC). The structures of individual copolyester macromolecules, including end-group chemical structures, were established using initially MALDI-TOFMS and then SEC/MALDI-TOFMS. The compositions of the copolyesters were determined by two methods, namely based on 1H NMR and MALDI-TOF spectra. The two sets of values showed good agreement. The sequence distribution was determined using the signal intensities of individual copolyester macromolecules, which appeared in MALDI-TOF mass spectra. Furthermore, sequence analysis gave information about the degree of transesterification. The copolyesters synthesized, with only one exception, were demonstrated to be almost random, which implies that the ester-ester exchange was close to completion.     

Electrospray ionisation tandem mass spectrometry of poly

Evaluation of polymer end-capping reactions with the aid of electrospray ionisation tandem mass spectrometry techniques (ESI-MS(n)) allows characterisation of novel poly[(R, S)-3-hydroxybutanoic acid]-(a-PHB) telechelics, containing primary hydroxyl groups at both polymer chain ends. The chemical structures of individual mass-selected macromolecules of the well-defined a-PHB telechelics have been defined in this way, and fragmentation mechanisms have been proposed. Copyright 1999 John Wiley & Sons, Ltd.     

Electrospray multistep ion trap mass spectrometry for the structural characterisation of poly

Electrospray 'soft' ionisation (ESI) and multistep mass spectrometry (MS(n)) techniques enable characterisation of a bioactive polymer, poly[(R,S)-3-hydroxybutanoic acid] (a-PHB), containing covalently bonded benzylpenicillin. The chemical structures of individual mass-selected bioactive macromolecules have been determined, and their fragmentation mechanisms have been compared with those of pure penicillin G. Copyright 2000 John Wiley & Sons, Ltd.     

Novel block copolymers of atactic PHB with natural PHA for cardiovascular engineering: Synthesis and characterization

Low-molecular weight macroinitiators derived from natural poly(3-hydroxyalkanoates) (PHAs), which contain olefinic and activated by 18-crown-6 ether carboxylic end groups, were used in anionic ring opening polymerization (ROP) of racemic β-butyrolactone and new diblock copolymers of selected PHAs (PHB, PHBV, PHO) with atactic poly[(R,S)-3-hydroxybutyrate] (a-PHB) were obtained. These novel copolymers were characterized using ¹H NMR, GPC and DSC. Hydrolytic degradation studies of selected copolymers were also performed. Finally, the suitability of these polymeric materials for cardiovascular engineering and as blend compatibilizers was demonstrated.     

Tough blends of poly(lactide) and amorphous poly([R,S]-3-hydroxy butyrate) – morphology and properties

Polylactide (PLA), a biodegradable polymer, produced from annually renewable natural resources, has a glass transition temperature in the range of 50–60 °C and is stiff and brittle at room temperature. In this communication we demonstrate that blending of PLA with atactic poly([R,S]-3-hydroxy butyrate) (a-PHB) leads to significant improvement of drawability and impact strength. The blends of PLA with a-PHB are biodegradable, similarly to plain PLA, and can be considered as a potential material for packaging, especially for food.     

Structural analysis of poly[(R,S)-3-hydroxybutyrate-co-L-lactide] copolyesters by electrospray ionization ion trap mass spectrometry

Two random copolyesters of poly[(R,S)-3-hydroxybutyrate-co-L-lactide] (P[(R,S)-3HB-co-LA]), prepared by equimolar reaction of (R,S)-beta-butyrolactone with L-lactic acid and (R,S)-3-hydroxybutyric acid with L-lactide, respectively, were characterized by electrospray ionization ion trap mass spectrometry (ESI-ITMS). Detailed studies of these copolyesters were performed by means of collision-induced dissociation (CID). The molecular architecture of individual copolyester macromolecules, including chemical structures of their end groups (hydroxyl and carboxylate), were established on the basis of their ESI mass spectra. The influence of an intermolecular transesterification reaction on the microstructure of the copolyester synthesized by equimolar reaction of (R,S)-3-hydroxybutyric acid with L-lactide was observed. The mass spectra provided information on sequence distribution and indicated that, despite the synthetic pathway applied, random P[(R,S)-3HB-co-LA] copolyesters were formed predominantly. The arrangements of comonomer structural units along the copolyester chains were evaluated by the respective ESI-MS/MS fragmentation pathways.     

The first enantiomerically pure [n]triangulanes and analogues: sigma-[n]helicenes with remarkable features

(M)-(-)- and (P)-(+)-Trispiro[2.0.0.2.1.1]nonanes [(M)- and (P)-3] as well as (M)-(-)- and (P)-(+)-tetraspiro[2.0.0.0.2.1.1.1]undecanes [(M)- and (P)-4]-enantiomerically pure unbranched [4]- and [5]triangulanes-have been prepared starting from racemic bicyclopropylidenecarboxylic [(1RS)-12] and exo-dispiro[2.0.2.1]heptane-1-carboxylic [(1RS,3SR)-13] acids. The optical resolutions of rac-12 and rac-13 furnished enantiomerically pure acids (S)-(+)-12, (R)-(-)-12, (1R,3S)-(-)-13, and (1S,3R)-(+)-13. The ethyl ester (R)-25 of the acid (R)-(-)-12 was cyclopropanated to give carboxylates (1R,3R)-26 and (1R,3S)-26. The ester (1R,3S)-26 and acids (1R,3S)-13 and (1S,3R)-13 were converted into enantiomerically pure methylene[3]triangulanes (S)-(-)- and (R)-(+)-28. An alternative approach consisted of an enzymatic deracemization of endo-[(1SR,3SR)-dispiro[2.0.2.1]heptyl]methanol (rac-20) or anti-[(1SR,3RS)-4-methylenespiropentyl]methanol (rac-18). This afforded (S)-(-)- and (R)-(+)-28 (starting from rac-20), as well as enantiomerically pure (M)-(-)- and (P)-(+)-1,4-dimethylenespiropentanes [(M)- and (P)-23] starting from rac-18. The methylenetriangulanes (S)-(-)- and (R)-(+)-28 were cyclopropanated furnishing (M)- and (P)-3. The rhodium-catalyzed cycloaddition of ethyl diazoacetate onto (S)-(-)- and (R)-(+)-28 yielded four diastereomeric ethyl trispiro[2.0.0.2.1.1]nonane-1-carboxylates in approximately equal proportions. The enantiomerically pure esters (1R,3S,4S)- and (1S,3R,4R)-30 were isolated by careful distillation and then transformed into [5]triangulanes (M)- and (P)-4 using the same sequence of reactions as applied for (M)- and (P)-3. The structures of the key intermediates (R)-12 and rac-31 were confirmed by X-ray analyses. Although [4]- and [5]triangulanes have no chromophore which would lead to any significant absorption above 200 nm, they have remarkably high specific rotations even at 589 nm with [alpha](20)D=-192.7 [(M)-3, c=1.18, CHCl(3))] or +373.0 [(P)-4, c=1.18, CHCl(3))]. This remarkable optical rotatation is in line with their helical arrangement of sigma bonds, as confirmed by a full valence space single excitation configuration interaction treatment (SCI) in conjunction with DFT computations at the B3LYP/TZVP//B3LYP/6-31+G(d,p) level of theory which reproduce the ORD very well. Thus, it is appropriate to call the helically shaped unbranched [n]triangulanes the "sigma-[n]helicenes", representing the sigma-bond analogues of the aromatic [n]helicenes.     

利用Reformatsky反应合成1-β-碳氢霉烯类抗生素中间体

以(2R)-3-[(3S,4R)-1-(叔丁基二甲基硅氧基)乙基]-4-乙酰氧基氮杂环丁-2-酮为母体,2-溴乙(丙)酸酯或2-溴丙酰胺为亲核试剂,通过Reformatsky反应合成了一系列新型的1-β-碳氢霉烯类抗生素中间体——3-{(2R)-2-[(3S,4R)-1-(叔丁基二甲基硅氧基)乙基]氮杂环丁-2-酮-4-基}乙(丙)酸酯(3a～3d)和3-{(2R)-2-[(3S,4R)-1-(叔丁基二甲基硅氧基)乙基]氮杂环丁-2-酮-4-基}-N,N-二取代丙酰胺(3e,3i和3k),其结构经1H NMR和13C NMR表征,其中3a～3e和3i未见文献报道。     

Endo entry to the nortricyclyl-norbornenyl cation system: stereochemistry in the fragmentation of endo-5-norbornenyl-2-oxychlorocarbene

Fragmentation of (S)-endo-5-norbornenyl-2-oxychlorocarbene [(S)-8] in cyclohexane-d12 gives approximately 20% (S)-endo-2-chloro-5-norbornene [(S)-7] with approximately 50% ee, 65-70% (R)-exo-2-chloro-5-norbornene [(R)-4] with >95% ee, and approximately 12% (R)-3-nortricyclyl chloride [(R)-5] with approximately 22% ee. (Analogous stereochemical results were also obtained starting with the enantiomeric carbene (R)-8.) The (S)-8 to (S)-7 and (S)-8 to (R)-4 conversions are ascribed mainly to retention and inversion S(N)i transition states, respectively. These have been located by computational methods and are nearly isoenergetic. In more polar solvents (CDCl3 and CD3CN), the fragmentation of (S)-8 increasingly occurs via competitive ion pair pathways in which steroselectivity is diminished, and escape to the norbornenyl-nortricyclyl cation directs the products away from endo-2-chloro-5-norbornene toward exo-chloride 4 and nortricyclyl chloride 5.     

Studies on the constituents of Broussonetia species. VII. Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, as inhibitors of glycosidase, from Broussonetia kazinoki SIEB

Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, were isolated from the branches of Broussonetia kazinoki SIEB, (Moraceae). Broussonetines M, O, P, and Q were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(10S)-10,13-dihydroxy-tri decyl]pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)9-oxo-13-hydroxy-3- tridecenyl]pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)10-oxo-13-hydroxy-3-++ +tridecenyl]pyrrolidine (3), and (2R,3S,4R,5R)-2-hydroxymethyl-3-hydroxy-4-(beta-D-glucopyranosyloxy++ +)-5-[10-oxo-13-(beta-D-glucopyranosyloxy)tridecyl]pyrrolidine (4) respectively, by spectroscopic and chemical methods. 1-4 inhibited beta-glucosidase, beta-galactosidase and beta-mannosidase.     

Poly(β-Amino acids). VI. Synthesis and conformational properties of poly[(r)-3-pyrrolidinecarboxylic acid]

Racemic and optically active 3-pyrrolidinecarboxylic acids (β-proline) were synthesized, and their polymers, poly[(RS)-β-proline] and poly[(R)-β-proline], were prepared by the polycondensation reaction of the p-nitrophenyl esters. Model compounds, N-cyclopentylcarboxylic acid pyrrolidide and N-cyclopentylcarbonyl-(R)-3-pyrrolidinecarboxylic acid pyrrolidide, were synthesized to elucidate the conformation of the polymer. The solution properties of poly[(R)-β-proline] and the model compounds were investigated by means of circular dichroism (CD) and NMR spectroscopy. The spectral patterns of the polymer and model compounds were similar in various solvents. Poly[(R)-β-proline] and poly[(RS)-β-proline] showed identical NMR spectra. These results suggest that poly[(R)-β-proline] may exist in a random conformation consisting of mixtures of cis and trans amide bonds. The conformational study of cyclopentanecarboxylic acid pyrrolidide by NMR spectroscopy with a shift reagent, Eu(fod)₃, in CDCl₃ implied that the plane containing the amide group bisects the cyclopentane ring. This suggests that each amide plane in the polymer in chloroform may also bisect the pyrrolidine ring.     

Five new nortropane alkaloids and six new amino acids from the fruit of Morus alba LINNE growing in Turkey

Investigation of the constituents of the fruits of Morus alba LINNE (Moraceae) afforded five new nortropane alkaloids (1-5) along with nor-psi-tropine (6) and six new amino acids, morusimic acids A-F (7-12). The structures of the new compounds were determined to be 2alpha,3beta-dihydroxynortropane (1), 2beta,3beta-dihydroxynortropane (2), 2alpha,3beta,6exo-trihydroxynortropane (3), 2alpha,3beta,4alpha-rihydroxynortropane (4), 3beta,6exo-dihydroxynortropane (5), (3R)-3-hydroxy-12-[(1S,4S)-4-[(1S)-1-hydroxyethyl]-pyrrolidin-1-yll-dodecanoic acid-3-O-beta-D-glucopyranoside (7), (3R)-3-hydroxy-12-[(1S,4S)-4-[(1S)-1-hydroxyethyl]-pyrrolidin-1-yll-dodecanoic acid (8), (3R)-3-hydroxy-12-1(1R,4R,5S)-4-hydroxy-5-methyl-piperidin-1-yll-dodecanoic acid-3-O-beta-D-glucopyranoside (9), (3R)-3-hydroxy-12-[(1R,4R,5S)-4-hydroxy-5-methyl-piperidin-1-yll-dodecanoic acid (10), (3R)-3-hydroxy-12-[(1R,4R,5S)-4-hydroxy-5-hydroxymethyl-piperidin-1-yl]-dodecanoic acid-3-O-beta-D-glucopyranoside (11), and (3R)-3-hydroxy-12-[(1R,4S,5S)-4-hydroxy-5-methyl-piperidin-1-yl]-dodecanoic acid (12) on the basis of spectral and chemical data.     

Structures of new ceramides from the fruit bodies of Grifola frondosa

Four new phytosphingosine-type ceramides, (2S,3S,4R)-2-[(2'R)-2'-hydroxydocosanoylamino]-1,3,4-octadecane triol (1), (2S,3S,4R)-2-[(2'R)-2'-hydroxytricosanoylamino]-1,3,4-octadecan etriol (2), (2S,3S,4R)-2-[(2'R)-2'-hydroxypentacosanoylamino]-1,3,4-octadec anetriol (3) and (2S,3S,4R)-2-[(2'R)-2'-hydroxyhexacosanoylamino]-1,3,4-octadeca netriol (4), have been isolated from the fruit bodies of Grifola frondosa. The structures of the new compounds were elucidated on the basis of their spectral data.     

Structural requirements in chiral diphosphine-rhodium complexes. VIII. Asymmetric hydrogenation of N-acetyldehydroamino acids with rhodium(I) complexes containing chiral carbocyclic analogues of DIOP.

Z--acetamidocinnamic acid was hydrogenated with neutral diphosphine-rhodium(I) complexes containing trans-1,2-bis(diphenylphosphinomethyl) cycloalkanes to give N-acetylphenylalanine: 86 % e.e.-(R) [(1R,2R)-cyclobutane]; 63 % e.e.-(R) [(1R,2R)-cyclopentane]; 35 % e.e.-(S) [(1S,2S)-cyclohexane]; and 82 % e.e.-(R) [(2R,3R)-DIOP]. Similarly, -acetamidoacrylic acid was hydrogenated to give N-acetylalanine: 72 % e.e.-(R) [(1R,2R)-cyclobutane]; 72 % e.e.-(R) [(1R,2R)-cyclopentane]; 40 % e.e.-(S) [(1S,2S)-cyclohexane]; and 73 % e.e.-(R) [(2R,3R)-DIOP].     

Studies on the constituents of Broussonetia species VIII. Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid, broussonetine U, from Broussonetia kazinoki Sieb

Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid, broussonetine U were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae) in low yield. Broussonetines R, S and T were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R)-1-hydroxy-3-[6-(4-hydroxybutyl)-cyclohexy-2-on-1(6)-enyllpropyl] pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,10S)-1,10,13-trihydroxytridecyl] pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,5S)-1,5, 13-trihydroxy-10-oxo-tridecyl] pyrrolidine (3). And broussonetines U and V were proposed to be (2S,3S,4S)-2-hydroxymethyl-3, 4-dihydroxy-5-(9-oxo-13-hydroxytridecyl)-5-pyrroline (4), (2R,3S,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)-9-oxo-13-hydroxy-3-tridecenyl] pyrrolidine (5), respectively, by spectroscopic and chemical methods.     

Total synthesis of two photoactivatable analogues of the growth-factor-like mediator sphingosine 1-phosphate: differential interaction with protein targets

The first synthesis of two photoreactive analogues of the lipid mediator and second messenger sphingosine 1-phosphate (S1P), [(32)P]-labeled (2S,3R)-14-O-(4'-benzoylphenyl)- and (2S,3R)-14-O-((4'-trifluoromethyldiazirinyl)phenyl)-(4E)-tetradecenyl-2-amino-3-hydroxy-1-phosphate, is described. The interactions of these probes with the S1P type-1 receptor (S1P(1)) transfected into membranes of rat hepatoma cells and with plasma proteins were analyzed. The S1P(1) receptor interacted in a specific manner with the benzophenone-containing ligand (K(D) = 84 +/- 10 nM vs K(D) for S1P = 36 +/- 2 nM); in contrast, no saturable specific binding was found with the diazirine-containing ligand. However, the same pattern was found for labeling of plasma proteins by both probes, indicating that different parts of the S1P pharmacophore underlie the interaction of S1P with its receptor and plasma carrier proteins.     

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.     

Hydrolysis and Desulfurization of the Diastereomeric Phosphoromonothioate Analogs of Uridine 2',3'-Cyclic Monophosphate

Hydrolyses of the two diastereomeric phosphoromonothioate analogs of uridine 2',3'-cyclic monophosphate [(R(P))- and (S(P))-2',3'-cUMPS] at 363.2 K have been followed by HPLC over pH-range 0-12. In aqueous alkali (pH > 9) only base-catalyzed endocyclic phosphoester hydrolysis to a nearly equimolar mixture of uridine 2'- and 3'-phosphoromonothioates (2'- and 3'-UMPS) takes place, analogously to the hydrolysis of uridine 2',3'-cyclic monophosphate (2',3'-cUMP). The (R(P))- and (S(P))-2',3'-cUMPS are hydrolyzed 50 and 30%, respectively, more slowly than 2',3'-cUMP. Under neutral and acidic conditions, desulfurization of the cyclic thiophosphates to 2',3'-cUMP competes with the phophoester hydrolysis, both reactions being acid-catalyzed at pH < 5. The desulfurization is most pronounced in strongly acidic solutions ([HCl] > 0.1 mol L(-)(1)), where more than 90% of the starting material is degraded via this route. At pH < 2, the thioates are considerably, i.e., more than 1 order of magnitude, more stable than 2',3'-cUMP. While the hydrolysis of 2',3'-cUMP is second-order in hydronium-ion concentration, that of 2',3'-cUMPS exhibits a first-order dependence. The reactivities of the two diastereomers are comparable with each other over the entire pH-range studied, the most significant difference being that the pH-independent desulfurization at pH > 5 is with the R(P)-isomer 5-fold faster than with the S(P)-isomer. In contrast to 2',3'-cUMP, depyrimidination of the starting material (i.e., release of the uracil base) competes with the hydrolysis of the thiophosphate moiety under neutral conditions (pH 6-8).     

Studies on the constituents of Broussonetia species X. Six new alkaloids from Broussonetia kazinoki Sieb.

Six new alkaloids, broussonetines W, X, M1, U1, J3, and J2 (1-6) were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae) as minor constituents. They were formulated as (2R,3R,4R,5R)-2-hydroxy-methyl-3,4-dihydroxy-5-17-(cyclohexy-2-on-1(6)-enyl)heptyllpyrrolidine (1), (2R,3S,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-17-(cyclohexy-2-on-1(6)-enyl)heptyl]pyrrolidine-4-O-beta-D-glucopyranoside (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(9R)-9,13-dihydroxytridecyl]- pyrrolidine (3), (2S,3S,4S)-2-hydroxymethyl-3,4-dihydroxy-5-(10-oxo-13-hydroxytridecyl)-5- pyrroline (4), (2R)-2-[(IS,2S)-1,2-dihydroxy-8-1(2R,3R,4R,5R)-5-(2-hydroxymethyl-3,4-dihydroxy-1-acetylpyrrolidinyl)loctyl]piperidine (5), (2R)-2-[(1S,2S)-1,2-dihydroxy-8-[(2R,3R, 4R,5R)-5-(2-hydroxymethy]-3,4-dihydroxypyrrolidinyl)]octyl]piperidine (6).     

Chiral Cyclopentane-Based Mimics of D-myo-Inositol 1,4,5-Trisphosphate from D-Glucose

Two routes from D-glucose to chiral, ring-contracted analogs of the second messenger D-myo-inositol 1,4,5-trisphosphate are described. Methyl alpha-D-glucopyranoside was converted by an improved procedure into methyl 4,6-O-(p-methoxybenzylidene)-alpha-D-glucopyranoside (6) and thence into methyl 2-O-benzyl-3,4-bis-O-(p-methoxybenzyl)-alpha-D-gluco-hexodialdopyranoside (1,5) (14) in four steps. In the first ring-contraction method 14 was converted into methyl 2-O-benzyl-6,7-dideoxy-3,4-bis-O-(p-methoxybenzyl)-alpha-D-gluco-hept-6-enopyranoside (1,5) (15), which on sequential treatment with Cp(2)Zr(n-Bu)(2) followed by BF(3).Et(2)O afforded a mixture of (1R,2S,3S,4R,5S)-3-(benzyloxy)-4-hydroxy-1,2-bis[(p-methoxybenzyl)oxy]-5-vinylcyclopentane (16) and its 4S,5R diastereoisomer 17. Removal of the p-methoxybenzyl groups of 16 and subsequent phosphorylation and deprotection afforded the first target compound, (1R,2R,3S,4R,5S)-3-hydroxy-1,2,4-tris(phosphonooxy)-5-vinylcyclopentane (3). In the second route, intermediate 14 was subjected to SmI(2)-mediated ring contraction to give (1R,2S,3S,4R,5S)-3-(benzyloxy)-4-hydroxy-5-(hydroxymethyl)-1,2-bis[(p-methoxybenzyl)oxy]cyclopentane (20). Benzylation of 20 provided (1R,2S,3S,4R,5S)-3-(benzyloxy)-6-[(benzyloxy)methyl]-4-hydroxy-1,2-bis[(p-methoxybenzyl)oxy]cyclopentane (22) and (1R,2S,3S,4R,5S)-3,4-bis(benzyloxy)-5-(hydroxymethyl)-1,2-bis[(p-methoxybenzyl)oxy]cyclopentane (21), which were elaborated to the target trisphosphates (1R,2R,3S,4R,5S)-3-hydroxy-5-(hydroxymethyl)-1,2,4-tris(phosphonooxy)cyclopentane (4) and (1R,2S,3R,4R,5S)-1,2-dihydroxy-3,4-bis(phosphonooxy)-5-[(phosphonooxy)methyl]cyclopentane (5), respectively. Both 3 and 4 mobilized intracellular Ca(2+), but 4 was only a few fold less potent than D-myo-inositol 1,4,5-trisphosphate, demonstrating that effective mimics can be designed that do not bear a six-membered ring.