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An oligodeoxynucleotide (ODN) containing a 2',2'-difluorinated analogue of a C4'-oxidized abasic site (C4'-OAS) was designed for the amine modification of biomolecules that interact with nucleic acids. In contrast to the parent C4'-OAS, which yielded amine-modified products accompanied by DNA strand scission, the ODN containing the difluoro C4'-OAS efficiently yielded products carrying ODNs. The amine modification proceeded without additional reagents being required and might be applicable to reactions in biological systems.

Introduction of the 2,2-dimethyl-4-phenylpiperazin-5-one scaffold into the P(3)-P(1) portion of the (2S,4S,5S)-5-amino-6-dialkylamino-4-hydroxy-2-isopropylhexanamide backbone dramatically increased the renin inhibitory activity without using the interaction to the S(3)(sp) pocket. Compound 31 exhibited >10,000-fold selectivity over other human proteases, and 18.5% oral bioavailability in monkey., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A 1,8-naphthalimide with [6]helicene derivative scaffold has been designed and synthesized. The (P)- and (M)-enantiomers of the [6]helicene derivative were resolved by HPLC on a chiral column. The single crystal of the [6]helicene derivative exhibits an intermolecular interactions of the 1,8-naphthalimide units., (This journal is © The Royal Society of Chemistry 2012)

Chiral cyclic α,α-disubstituted amino acids, (3S,4S)- and (3R,4R)-1-amino-3,4-(dialkoxy)cyclopentanecarboxylic acids ((S,S)- and (R,R)-Ac(5)c(dOR); R: methyl, methoxymethyl), were synthesized from dimethyl L-(+)- or D-(-)-tartrate, and their homochiral homoligomers were prepared by solution-phase methods. The preferred secondary structure of the (S,S)-Ac(5)c(dOMe) hexapeptide was a left-handed (M) 3(10) helix, whereas those of the (S,S)-Ac(5)c(dOMe) octa- and decapeptides were left-handed (M) α helices, both in solution and in the crystal state. The octa- and decapeptides can be well dissolved in pure water and are more α helical in water than in 2,2,2-trifluoroethanol solution. The left-handed (M) helices of the (S,S)-Ac(5)c(dOMe) homochiral homopeptides were exclusively controlled by the side-chain chiral centers, because the cyclic amino acid (S,S)-Ac(5)c(dOMe) does not have an α-carbon chiral center but has side-chain γ-carbon chiral centers., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Four types of α,α-disubstituted amino acids {i.e., α-aminoisobutyric acid (Aib), 1-aminocyclopentanecarboxylic acid (Ac(5)c), (3S,4S)-1-amino-(3,4-dimethoxy)cyclopentanecarboxylic acid [(S,S)-Ac(5)c(dOM)] and its enantiomer (R,R)-Ac(5)c(dOM)} were introduced into l-leucine-based hexapeptides and nonapeptides. The dominant conformations of eight peptides: Cbz-(L-Leu-L-Leu-dAA)(2)-OMe [dAA = 1: Aib; 2: Ac(5)c; 3: (S,S)-Ac(5)c(dOM); 4: (R,R)-Ac(5)c(dOM)] and Boc-(L-Leu-L-Leu-dAA)(3)-OMe [dAA = 5: Aib; 6: Ac(5)c; 7: (S,S)-Ac(5)c(dOM); 8: (R,R)-Ac(5)c(dOM)], were investigated by IR, CD spectra and X-ray crystallographic analysis. The CD spectra revealed that Aib hexapeptide 1 and Ac(5)c hexapeptide 2 formed right-handed (P) 3(10)-helices, while Ac(5)c(dOM) hexapeptides 3 and 4 formed a mixture of (P) 3(10)- and α-helices. The Aib nonapeptide 5 formed a (P) 3(10)-helix, the Ac(5)c nonapeptide 6 formed a mixture of (P) 3(10)- and α-helices, and the Ac(5)c(dOM) nonapeptides 7 and 8 formed (P) α-helices. X-Ray crystallographic analysis revealed that the Aib hexapeptide 1 formed a (P) 3(10)-helix, while (S,S)-Ac(5)c(dOM) hexapeptide 3 formed a (P) α-helix. In addition, the Ac(5)c nonapeptide 6 and (R,R)-Ac(5)c(dOM) nonapeptide 8 formed (P) α-helices. The Aib and achiral Ac(5)c residues have the propensity to form 3(10)-helices in short peptides, whereas the chiral Ac(5)c(dOM) residues have a penchant for forming α-helices.

Bisphosphonates have high affinity for hydroxyapatite (HA), which is abundantly present in bone. Also, platinum complexes are known that have a wide spectrum of antitumor activities. The conjugate of bisphosphonate and a platinum complex might have HA affinity and antitumor activity, and become a drug for metastatic bone tumor. In this study, the authors synthesized platinum complexes that had dialkyl bisphosphonic acid as a ligand, and evaluated the possibility of the synthesized complexes as a drug for metastatic bone tumor. The synthesized dialkyl bisphosphonate platinum(II) complex was characterized, and its stability in an aqueous solution was also confirmed. The synthesized platinum complex showed higher HA affinity than other platinum complexes such as cisplatin and carboplatin in an experiment of adsorption to HA. In vitro, the platinum complex showed tumor growth inhibitory effect stronger than or equal to cisplatin, which is the most commonly used antitumor agent. Moreover, the platinum complex showed a bone absorption inhibitory effect on the osteoclast. These results suggest potential of dialkyl bisphosphonate platinum(II) complexes as a drug for metastatic bone tumor.

A single chiral cyclic α,α-disubstituted amino acid, (3S,4S)-1-amino-(3,4-dimethoxy)cyclopentanecarboxylic acid [(S,S)-Ac(5)c(dOM)], was placed at the N-terminal or C-terminal positions of achiral α-aminoisobutyric acid (Aib) peptide segments. The IR and (1)H NMR spectra indicated that the dominant conformations of two peptides Cbz-[(S,S)-Ac(5)c(dOM)]-(Aib)(4)-OEt (1) and Cbz-(Aib)(4)-[(S,S)-Ac(5)c(dOM)]-OMe (2) in solution were helical structures. X-ray crystallographic analysis of 1 and 2 revealed that a left-handed (M) 3(10)-helical structure was present in 1 and that a right-handed (P) 3(10)-helical structure was present in 2 in their crystalline states., (Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.)

Chiral cyclic alpha-amino acid containing oligopeptide catalyzed highly enantioselective epoxidation of alpha,beta-unsaturated ketones and the alpha-helical secondary structure of the peptide catalyst were revealed by X-ray crystallographic analysis.

Asymmetric intermolecular hydroacylation between salicylaldehyde (1) and 1,5-hexadiene (2) using a combination of [RhCl(C(8)H(14))(2)](2) (0.10 eq), (S)-BINAP (0.10 eq), and ZnBr(2) (0.20 eq) afforded an enantiomerically enriched hydroacylated product iso-3 of 84% ee, along with an achiral product normal-3.

Two series of homooligomers composed of diastereoisomeric cyclic alpha-amino acids having two chiral centers at the alpha-carbon and the side chain were synthesized, and their preferred secondary structures were studied in solution and in the crystal state. The oligomers are a new class of helical-foldamers possessing two kinds of chiral centers on the helical backbone and at the lateral surface of the helix.

5-Uridine derivative carrying a TEMPO radical (UST) was prepared and its single strand (ssUST) and a double strand (dsUST) with its complementary strand were obtained. Similarly, single strands carrying two and five radicals (ssUST2 and ssUST5, respectively) and the corresponding double strands (dsUST2 and dsUST5) were prepared. Their electron paramagnetic resonance (EPR) spectra showed typical anisotropic broadening in the high field line. The rotational correlation times, tau(R), estimated by analyzing the EPR spectra are 1.1 x 10(-10), 5.9 x 10(-10), and 14 x 10(-10) s for UST, ssUSTm, and dsUSTm, respectively. The water-proton relaxivities, r(1) and r(2), at 25 MHz, 0.59 T, and 25 degrees C, also increased in the same order and the r(1) values were 0.26, 0.41, and 0.56 mM(-1) s(-1) for UST, ssUSTm, and dsUSTm, respectively. The r(1) values of 1.00 and 2.06 mM(-1) s(-1) for dsUST2 and dsUST5, respectively, were obtained., (2008 John Wiley & Sons, Ltd.)

Non-invasive measurement and visualization of free radicals in vivo would be important to clarify their roles in the pathogenesis of free radical-associated diseases. Nitroxyl radicals can react with free radicals and be derivatized to achieve specific cellular/subcellular localizing capabilities while retaining the simple spectral features useful in imaging. Overhauser-enhanced magnetic resonance imaging (OMRI), which is a double resonance technique, creates images of free radical distributions in small animals by enhancing the water proton signal intensity via the Overhauser Effect. In this study, we synthesized various nitroxyl probes having (15)N nuclei and deuterium, and measured the enhancement factor for Overhauser-enhanced magnetic resonance imaging experiments. (15)N-D-4-Oxo-2,2,6,6-tetramethylpiperidine-1-oxyl ((15)N-D-oxo-TEMPO) has the highest enhancement factor compared with other nitroxyl probes. The proton signal enhancement was higher for (15)N-labeled nitroxyl probes when compared to the (14)N-labeled analogues because of the reduced spectral multiplicity of the I=1/2 nucleus. Furthermore, this enhancement is proportional to the line width and number of electron spin resonance lines of nitroxyl radicals. Finally, we compared the Overhauser-enhanced magnetic resonance image of (15)N-labeled, deuterated 4-Oxo-2,2,6,6-tetramethylpiperidine-1-oxyl with that of (14)N-H-TEMPOL. These results suggested that the selective deuteration of the nitroxyl probes enhanced the signal-to-noise ratio and thereby improved spatial and temporal resolutions.

Bleomycin-induced oxidative DNA damage under limited oxygen conditions results in the formation of the C4'-oxidized abasic site (1). We synthesized the oligodeoxynucleotides (ODN) 5, which contains 4'-o-nitrobenzyloxythymidine (3), and 6, which contains 2-nitrobenzyloxy-4'-methoxy-2'-deoxy-d-ribofuranoside (4), as the caged precursors of 7, an ODN containing 1, to study its reactivity with amines. Photoirradiation of the single- and double-stranded 5 led to the formation of 7. Uncaging of the duplex was faster and the yield of 7 was higher with the double-stranded than with the single-stranded ODN. It was suggested that a low dielectric environment of the o-nitrobenzyloxy group in the minor groove of the duplex might accelerate the uncaging rate. Similarly, 6 and its duplex yielded 7 by photoirradiation. However, the yields of 7 were lower than those of 5, and duplex formation slowed the uncaging rate. Reaction of the obtained 7 with an amine resulted in the formation of the lactam 2b in good yield in both single- and double-stranded forms, showing that amine modification of biomolecules by an ODN containing 1 is possible under physiologic conditions.

Chiral cycloalkane-trans-1,2-diols (+/-)-3 and (+/-)-8 having a diester moiety have been prepared from dimethyl dialkenylmalonate using olefin metathesis by Grubbs catalyst, followed by epoxidation and acidic hydrolysis. Kinetic resolution of racemic cyclopentane-trans-1,2-diol (+/-)-3 by lipase-catalyzed transesterification afforded an optically active monoacetate (-)-5 of 95% ee in 46% yield and the recovered diol (-)-3 of 92% ee in 51% yield, and that of cycloheptane-trans-1,2-diol (+/-)-8 gave a monoacetate (+)-10 of 95% ee in 51% yield and the diol (-)-8 of >99% ee in 43% yield, respectively. The enantiomer selectivity of racemic cyclic trans-1,2-diols bearing a diester moiety by lipases (Amano PS and Amano AK) was opposite to that of the reported simple racemic cycloalkane-trans-1,2-diols. To explain the lipase-catalyzed enantiomer selectivity, computer modeling of lipase-substrate complexes was performed. Furthermore, the optically active diester (-)-8 could be efficiently converted into an optically active seven-membered-ring alpha,alpha-disubstituted amino acid (4R,5R)-(-)-15.

L-Leu hexapeptide containing alpha-aminoisobutyric acid (Aib) forms a right-handed (P) 3(10)-helix, whereas that containing cyclic alpha,alpha-disubstituted amino acid Ac(5)c(dOM) assumes a right-handed (P) alpha-helix in the solid state.

Rh-catalyzed intermolecular hydroacylation between salicylaldehyde and alkenylnitriles proceeded at room temperature to preferentially give normal-hydroacylated products. Addition of CH3CN and NaOAc accelerated the Rh-catalyzed hydroacylation of monoolefins to exclusively produce the normal-hydroacylated products under mild reaction conditions. Plausible mechanisms for the regioselections are also described.

[Structure: see text] We synthesized oligodeoxynucleotide (ODN, 3), which contains 4'-o-nitrobenzyloxythymidine (4) as a caged precursor of C4'-oxidized abasic site (1). Photoirradiation of 3 at 365 nm followed by amine treatment under neutral conditions afforded the lactam (2) efficiently. Duplexed ODN 3 was converted to 1 faster and more efficiently than single stranded 3, whereas amine treatment of 1 formed from single stranded 3 resulted in slightly faster lactam formation than with the duplex.

We studied photochemical generation of oligodeoxynucleotide (ODN) containing C4'-oxidized abasic site (1) from its caged precursor 3. Photoirradiation of 3 at 365 nm followed by amine treatment under neutral conditions afforded the lactam (2) efficiently. Duplexed ODN 3 was converted to 1 faster and more efficiently than single stranded 3, whereas amine treatment of 1 formed from single stranded 3 resulted in slightly faster lactam formation than with duplex.

Both diastereomeric right-handed (P) and left-handed (M) 310-helices exist in homopeptides having twelve chiral centers at the side-chain bicyclic skeletons.

A method for the generation of ODNs containing a C4'-oxidized abasic site (C4'-OAS) from "photocaged" ODNs was investigated. We synthesized C4'-caged ODN 1 and C1'-caged ODN 2 bearing an o-nitrobenzyloxy group at the C-4' position and the C-1' position, respectively. The duplex stabilities of 1 and 2, with their complementary ODNs were studied by Tm measurements. The photochemical reaction of 1 and 2 to generate ODN 3 containing C4'-OAS, and the subsequent amine modification reaction were studied.

Oligodeoxynucleotide (ODN; 1) containing 2-N-tert-butylaminoxyladenosine (2) was synthesized by the conventional phosphoramidite method. The thermal stability and structure of the duplex of ODN 1 and the complementary strand were elucidated by UV-melting temperature measurements and CD experiments. In phosphate buffer, ODN 1 showed a three line EPR spectrum. Upon duplex formation, the EPR spectrum of 1 changed which indicates that EPR spectra of 1 can provide information on structures of ODN.

Intermolecular hydroacylation between salicylaldehydes 1, 26-40 and 1,4-penta- or 1,5-hexadienes 4-13 by Rh-catalyst proceeded under mild reaction conditions to give a mixture of iso- and normal-hydroacylated products 14-25, 41-55, and 57-60. In the hydroacylation reaction, chelation of both salicylaldehyde and diene to the Rh-complex plays a crucial role. The ratio of iso- and normal-hydroacylated products could be regulated by the addition of salicylic acid or amines. The effects of various Rh-complexes, solvents, and additives were examined, and the plausible mechanisms of the catalytic cycle were proposed on the basis of the deuterium-labeling salicylaldehyde experiments.

N-tert-Butylaminoxyl nucleosides (1 and 2) were synthesized starting from 6-chloropurine derivative (3). These compounds are expected as a new tool to elucidate structure of DNA. Their properties and pH-dependent change of EPR spectra were studied.

We synthesized oligonucleotide (1) containing 4'-o-nitrobenzyloxythymidine (2), which was prepared by reaction of 4',5'-unsaturated thymidine with m-CPBA followed by Lewis-acid catalyzed addition of o-nitrobenzylalcohol. The duplex stability of 1 with the complementary oligonucleotide was studied by Tm measurement. Photochemical reaction of 1 to generate C4'-oxidized abasic site containing oligonucleotide (3) was studied.

Optically active peptide foldamers Tfa-[(S)-(alphaEt)Leu]-[(S)-(alphaEt)Nva]-Deg-[(S)-(alphaEt)Nle]-OEt (10) and Tfa-[(S)-(alphaEt)Val]-[(S)-(alphaEt)Leu]-[(S)-(alphaEt)Nva]-Deg-[(S)-(alphaEt)Nle]-OEt (11) composed of diverse alpha-ethylated alpha,alpha-disubstituted alpha-amino acids were synthesized. The dominant conformation of these peptides in solution was an unusual, fully extended planar conformation, and that in the crystal state was both right-handed (P) and left-handed (M) 3(10)-helical structures in 10 and a P 3(10)-helical structure in 11, respectively. The preferred planar C(5) conformation of the peptides prepared from chiral alpha-ethylated alpha,alpha-disubstituted alpha-amino acids was drastically different from the 3(10)-helical structure of the peptides prepared from chiral alpha-methylated alpha,alpha-disubstituted alpha-amino acids.

The 7,8-bis(benzyloxy)bicyclo[2.2.2]octa-2,5-diene derivatives have been synthesized via Diels-Alder reaction of optically active 5,6-bis(benzyloxy)cyclohexa-1,3-diene and dienophiles. The corresponding tricarbonyliron complexes have also been synthesized in enantiomerically pure form.

Treatment of the sodium salt of 2'-deoxy-3', 5'-bis-O-(tert-butyldimethylsilyl)-5-iodouridine (3) with n-BuLi effected regioselective lithiation at the 5-position and the following reaction with various electrophiles afforded 5-substituted 2'-deoxyuridines including 1b, the precursor of stable spin-labeled 1a, in good yields.

We synthesized 5-N-tert-butylhydroxylamino-2'-deoxyuridine (9b) via lithium-halogen exchange reaction of sodium salt of 5-iodo-2'-deoxyuridine (8b). This procedure was applicable to synthesis of the corresponding uridine (9a) and N-benzoyl cytidine (13). Obtained 9b was converted into stable aminoxyl (5a) by treatment with Ag2O to study its properties as a novel spin-labeled nucleoside.

Novel purine nucleosides with a N-tert-butylhydroxylamino group at the 2-position of purine nucleus (1-3) were synthesized, which might prefer anti conformation and would not perturb DNA structure when incorporated into oligonucleotide. Oxidation of 1-3 by treatment with Ag2O or air afforded stable aminoxyl radicals (1'-3') and their properties were studied by EPR spectroscopy. 5-N-tert-butylhydroxylamino uridine (4) was also synthesized.

We identified a novel metabolic system of morphine in the opium poppy (Papaver somniferum L.). In response to stress, morphine is quickly metabolized to bismorphine consisting of two morphine units, followed by accumulation in the cell wall. This bismorphine binds predominantly to pectins, which possess high galacturonic acid residue contents, through ionical bonds. Our newly developed method using artificial polysaccharides demonstrated that bismorphine bridges are formed between the two amino groups of bismorphine and the carboxyl groups of galacturonic acid residues, resulting in cross-linking of galacturonic acid-containing polysaccharides to each other. The ability of bismorphine to cross-link pectins is much higher than that of Ca2+, which also acts as a cross-linker of these polysaccharides. Furthermore, we confirmed that cross-linking of pectins through bismorphine bridges leads to resistance against hydrolysis by pectinases. These results indicated that production of bismorphine is a defense response of the opium poppy. Bismorphine formation is catalyzed by anionic peroxidase that pre-exists in the capsules and leaves of opium poppies. The constitutive presence of morphine, together with bismorphine-forming peroxidase, enables the opium poppy to rapidly induce the defense system.

An eight-membered cyclic beta-amino acid, 8-aminocyclooct-4-enecarboxylic acid, was designed as a conformationally restricted non-proteinogenic amino acid. A hybrid tripeptide containing this eight-membered cyclic beta-amino acid and 2-aminoisobutyric acids was synthesized by conventional solution methods. The conformation of the tripeptide was studied using X-ray analysis and was shown to form an eleven-membered hydrogen-bonded turn (3(11)-helical structure) in the solid state.

We designed a new type of spin-labeled nucleosides with an N-tert-butylaminoxyl radical which is introduced to the nucleobase directly. Purine and pyrimidine ribonucleosides containing the aminoxyl radical such as 1a-d, 2, 3, and 4 were synthesized to investigate the stability and behavior of the N-tert-butylaminoxyl radical on a nucleobase. Lithiation of tri-O-silylated 6-chloropurine ribonucleoside (5) followed by reaction with 2-methyl-2-nitrosopropane (MNP) gave the key compound 6a, which was further converted to 6b-d. Oxidation of the obtained 6a-d and their triols (7a-d) with Ag(2)O led to formation of the corresponding stable spin-labeled nucleosides (8a-d and 1a-d), which were confirmed by EPR spectroscopy. Similarly, the precursors of spin-labeled pyrimidines (13, 20, and 23) were synthesized by site-selective lithiation of tri-O-protected pyrimidine derivatives (9, 18, and 21) followed by the reaction with MNP and deprotection. An EPR study showed that the aminoxyl radicals (2, 3, and 4) were stable and that their hyperfine structures were dependent on the position of the radical. Electron densities of pyrimidine also affected hyperfine structures.

Diastereoselective alkylation of ethyl 2-methyl- and/or 2-ethylacetoacetates using the (S,S)-cyclohexane-1,2-diol as an acetal chiral auxiliary afforded enol ethers (2a-f and 5a-f) of 92->95% de in 31-70% yields. Removal of the cyclohexane-1,2-diol with BF(3)-OEt(2) afforded beta-keto esters (3 and 6) bearing a chiral quaternary carbon. The beta-keto esters could be easily converted into optically active alpha-methylated and/or alpha-ethylated alpha,alpha-disubstituted amino acids (12 and 13) in 21-99% yields using Schmidt rearrangement.

Novel spin-labeled ribonucleosides 1-5 were synthesized to investigate stability and behavior of N-tert-butyl aminoxyl radical on nucleobase. Site selective lithiation of tri-O-protected ribonucleosides followed by the reaction with 2-methyl-2-nitrosopropane (MNP) resulted in introduction of N-tert-butylhydroxylamino group into various positions of purine or pyrimidine nucleus. Oxidation of the obtained hydroxylamines with Ag2O led to formation of 1-5. EPR study showed that the unpaired electron of the aminoxyl radical was delocalized into the nucleobase and hyperfine structures were dependent on the position of the radical.

Rh-Catalyzed cyclization was applied to the formation of a chiral quaternary carbon. It has become clear that the Rh-complex can discriminate between isopropenyl and 2-isopentenyl (or isopentyl) substituents, and the cyclization afforded 3,3,4-trisubstituted cyclopentanones with a chiral quaternary carbon in a stereoselective manner. The cyclization of 4-pentenals 6a, b by an achiral neutral Rh(PPh3)3Cl afforded 3,3,4-cis-trisubstituted cyclopentanones (+/-)-7a,b in 86-96%, and the cyclization by a cationic Rh[(R)-BINAP]CIO4 afforded 3,3,4-trans-trisubstituted cyclopentanones (-)-8a, b of 82-86% ee in 88-98% yields. The mechanism of stereoselection by Rh-complexes is also discussed.

Asymmetric spirocyclization based on intramolecular conjugate addition using a combination of a Lewis acid and an optically active cyclohexane-1,2-diol has been studied in connection with 1) the effect of substituents on the cyclohexane-1,2-diol and 2) the effect of substituents on the substrate. This reaction was found to be both thermodynamically and kinetically controlled under restricted conditions.

Asymmetric cyclization of symmetrical 3,4-disubstituted and 3,3, 4-trisubstituted 4-pentenals was studied using Rh-complexes with chiral ligands. The cyclization of symmetrical 4-pentenals 4a,b by a neutral Rh[(R)-BINAP]Cl afforded cis-3,4-disubstituted (4R)-cyclopentanones 9a,b of >95% ee in 25-31% yields; on the other hand, the cyclization of 4a-c by a cationic Rh[(R)-BINAP]ClO(4) afforded trans-3,4-disubstituted (4S)-cyclopentanones 10a-c of >95% ee in 70-81% yields. All stereoisomers could be stereoselectively made by the selection of a neutral or cationic Rh-complex, and (R)- or (S)-BINAP ligand. The Rh-catalyzed cyclization could be applied to the construction of cyclopentanones 17 and 18 bearing a chiral quaternary carbon. The cyclization by the cationic Rh[(R)-BINAP]ClO(4) afforded the optically active trans-3,3, 4-trisubstituted cyclopentanones 18a-c of 92-95% ee in 75-83% yields. The catalytic cycle was also studied by using deuterium aldehyde, and the tentative mechanisms of the enantio- and diastereoselection were proposed.

A novel method of preparing C-4' oxidized nucleotide, a monomeric model of an alkali labile lesion (1) has been studied. The C-4' selenated 4a and 4b were found to be effective in preparing 3, a monomeric model of 1, by the reaction with NBS (N-bromosuccinimide). The successive reaction of 3 with amine at room temperature afforded the alpha,beta-unsaturated gamma-methylene-gamma-lactam (2) in good yield.

The reactivity of 3-substituted 4-methyl-4-(3-oxobutyl)-2-cyclohexen-1-ones (1) in the presence of a combination of a Lewis acid and a 1,2-diol was studied. The results suggest several factors that influence 6-membered ring formation, including two types of intramolecular aldol reaction and intramolecular 1,4-addition, due to the C3-substituent, Lewis acid, and the presence of diol. In this study, novel methodology to prepare two types of decalin skeleton could be developed.

Conformational energy computations on a homo-hexapeptide of (S)-isovaline were performed using molecular mechanics on MacroModel. Conformational search calculations were carried out by Monte Carlo method. AMBER* was used as the force field. The global minimum energy conformation was found to be a 3(10)-helix coordinated by four hydrogen bonds. The results of the theoretical analysis of the conformation of the peptide are in agreement with its reported conformational properties in the solid state determined by X-ray crystallographic analysis.

7-Substituted norbornadienes were stereoselectively converted into the meso-3,5-bis(acetoxymethyl)cyclopentenes by a three-step sequence of ozonolysis, reduction, and acetylation. Rhizopus delemar lipase (RDL)-catalyzed asymmetric hydrolysis of meso-3,5-bis(acetoxymethyl)cyclopentenes afforded the monoalcohols of high enantiomeric purities (>95% ee) in good yields (64-95%). The obtained monoalcohols 11 and 14 could be applied for the synthesis of antiviral carbocyclic nucleosides (-)-carbovir and (-)-BCA.

This paper describes the preparation of the polyfunctionalized cyclopentane ((+/-)-5) by silica gel-catalyzed air-oxidation, and its kinetic resolution by means of microbial reduction with Rhodotorula rubra to afford optically pure (-)-5 (greater than 99% ee). Starting with (-)-5, a new route to prostaglandin E1 was established.

A series of new purine ribonucleoside derivatives having oxyalkyl or amidoalkyl functionality at the 6-position have been synthesized from nebularine tri-O-benzoate by Miniscitype homolytic processes using ammonium persulfate as the radical initiator.