Synthesis and Structural Analysis of Higher Analogs of Sucrose

ABSTRACT

Three sucrose monoalcohols with free hydroxyl groups at C-1', C-6, and C-6' (1, 4, and 6) were prepared selectively and in good yield from 2,3,3',4,4'-penta-O-benzylsucrose. These compounds were oxidized to aldehydes and reacted with stabilized ylide, Ph₃P=CHCO₂Me to afford appropriate α,β-unsaturated esters 10, 11, and 12. Each olefin was cis-hydroxylated with OsO₄/NMO to stereoisomeric diols 13/14, 15/16, and 17/18, configurations of which were assigned by chemical correlation and CD evaluation. Stereoselectivity of the osmylation reaction was surprisingly low (ca 3:2), especially as compared to a similar process performed on simple derivatives of 6,7-unsaturated methyl glycosides for which the ratio of isomeric diols was assigned as 10:1. The osmylation of 11 (derivative homologated by a C₂-unit at the glucose part) did not obey Kishi's rule. Horner-Emmons reaction of sucrose aldehyde 7 with a sugar-derived phosphonate 22 afforded α,β-unsaturated derivative 24, homologated by a C₇-unit at the glucose end.     

Higher Sucrose Analogs: Homologation of a Glucose Unit of Sucrose by Two Carbon Atoms

Abstract

The primary hydroxyl groups (at C-6 and C-6′) in 2,3,4,3′4′-penta-O-benzyl-l′-O-methoxymethyl sucrose (2) can be reactively differentiated with tert-butyldiphenylsilyl chloride. Reaction of 2 with TBDPSCl afforded only one monosilylated product protected at C-6′ (6). The regioisomeric monoprotected sucrose 8 was prepared by selective deprotection of the double silylated derivative 7. Compound 6 was converted into 2,3,4,3′,4′-penta-O-benzyl-6-carbomethoxymethylidene-1′-O-methoxymethylsucrose 10 in three steps. Osmylation of the double bond in 10 afforded stereoisomeric homologated sucroses: 11a [6(S),7(R)] and 11b [6(R),7(S)] in the ratio 3:2. A large downfield shift of the H-1 (up to 0.5 ppm) was observed for 6′-silylated derivatives.     

The Role of the C-3 Substituent in the Asymmetric Dihydroxylation of Hexo-5-Enofuranosides

ABSTRACT

Asymmetric dihydroxylation of vinyl furanosides 1-6 by use of OsO₄, AD-mix-α® and β® is described yielding the corresponding hexofuranose sugars. Vinyl furanosides 2 and 3, with an ester group at C-3, and vinyl manno furanoside 5 on asymmetric dihydroxylation with AD-mix α® exhibited high R diastereoselectivity at C-5. Reversal in diastereoselectivity at C-5 was observed for the 3-deoxy vinyl furanoside 6 giving furanosaccharide 6S with the S configuration at C-5.     

Acid-Catalyzed E-Ring Expansion and Isomerization of 3-Acetylbetulin: Synthesis of Cytotoxic Anhydrobetulin Saponins

22(17 → 28)abeo-Lupene derivatives 5a and 6a were obtained after the acid-catalyzed E-ring expansion of 3-acetylbetulin (1a). Glycosylation of these dehydrated triterpenoids using Schmidt's trichloroacetimidate sugar donors in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) provided the new anhydrobetulin saponins 7b–7e in which the terminal olefin C-20(29) isomerizes to form a C-19 tetrasubstituted alkene. The preliminary cytotoxic evaluation revealed that saponins 7b–7d exhibited a moderate cytotoxic activity against A549, DLD-1, and WS1 human cell lines with IC₅₀ ranging from 22 to 49 μM.     

Synthesis and structural studies of C-5 aryl- and C-6 alkyl-substituted pyrimidine derivatives

C-5 and C-6 disubstituted pyrimidine derivatives 2–7 were synthesized. Introduction of the aryl rings at C-5 of pyrimidine moiety in 5 and 6 was performed using palladium-catalyzed Stille cross-coupling reaction. The novel C-6 fluorophenylalkylated 5-phenylpyrimidine derivative (7) was prepared by lithiation of 5-phenylpyrimidine (6) and subsequent reaction of thus obtained organolithium intermediate with p-fluoroacetophenone. The structures of 3, 4 and 6 were determined by X-ray crystal structure analysis. Both methoxy groups in these structures adopt a synperiplanar conformation with respect to the N1 and N3 atoms of the pyrimidine ring. The molecules of 3 and 4 are linked through weak Br···Br interactions into zig-zag chains. The molecules of 6 are assembled into layers by one C–H···O hydrogen bond, C–H···π and aromatic π···π stacking interactions.     

Synthesis of (2S,3R,1'R)-stegobinone,the pheromone of the drugstore beetle,with stereocontrol at C-2 and C-1'

(2$\text{S}$,3$\text{R}$,1'$\text{R}$)-Stegobinone [2,3-dihydro-2,3,5-trimethyl-6-(1'-methyl-2'-oxobutyl)-4H-pyran-4-one], the pheromone of $\text{Stegobium}$ $\text{paniceum}$ L., was synthesized with stereocontrol at C-2 and C-1' starting from ethyl ($\text{R}$)-3-hydroxybutanoate and methyl ($\text{R}$)-3-hydroxy-2-methylpropanoate. The dihydro-γ-pyrone ring of the pheromone was constructed by an intramolecular acylation followed by acid-catalyzed cyclization.     

trans-Tetradec-2-enoic Acid in Impatiens glandulifera

Purification of the hydrophobic extracts of the flowers and seed pods of Impatiens glandulifera(Himilayan balsam) yielded 2-methoxy-[1,4]-naphthoquinone 1, 1-hydroxyeicosan-3-one 16, and an unusual unsaturated fatty acid, trans-tetradec-2-enoic acid 6. Mass spectrometry and nuclear magnetic resonance spectroscopy indicated that the latter compound (6) was isolated as a mixture with linolenic acid 8 and saturated acids 7, 9, and 10 (chain lengths C-16, 18, and 20). Its structure was subsequently proven by independent chemical synthesis.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Synthesis and antimicrobial activity of new derivatives of pyrano[4',3':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidine and new heterocyclic systems

Taking into account previously obtained biological results on some polyheterocyclic compounds (containing different heteroatoms) and in particular on several 8-amino-5-isopropyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines Ia-v we have carried out the synthesis of twentyone 8-amino-5-isobutyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines 6. Therefore we have slightly modified the structure of the previously studied I introducing at C-5 an isobutyl group instead of the previously examined isopropyl ones in order to see if this variation (changing a little the lipophilicity) will affect the biological activity. Furthermore thieno[3,2-d]pyrimidine-8-thione 7 and their S-alkylated 8 were synthesized. Finally by alkylation of 5-isobutyl-2,2-dimethyl-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-8(9H)-one 3 with alkyl dichlorides (bifunctional reagents) we realized the cyclization of a thiazole or thiazine ring on the [b] side of the pyrimidine ring with formation of the new condensed pentaheterocyclic systems: pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d][1,3]thiazolo[3,2-a]pyrimidin-8-one 11 and pyrano[4''',3''':4'',5'']pyrido[3'',2'':4',5']thieno[3',2':4,5]pyrimido[2,1-b][1,3]thiazin-8-one 12. It was found that some of the synthesized compounds showed interesting antimicrobial activity (by agar diffusion method) against some gram-positive and gram-negative bacilli strains.     

Comprehensive structure characterization of lipid a extracted from <Emphasis Type="Italic">Yersinia pestis</Emphasis> for determination of its phosphorylation configuration

We report on comprehensive structure characterization of lipid A extracted from Yersinia pestis (Yp) for determination of its phosphorylation configuration that was achieved by combining the methods of molecular biology with high-resolution tandem mass spectrometry. The phosphorylation pattern of diphosphorylated lipid A extracted from Yp has recently been found to be a heterogeneous mixture of C-1 and C-4′ bisphosphate, C-1 pyrophosphate, and C-4′ pyrophosphate (Proc. Natl. Acad. Sci. 2008, 105, 12742). To reduce the inherent phosphate heterogeneity of diphosphorylated lipid A extracted from Yp, we incorporated specific C-1 and C-4′ position phosphatases into wild type KIM6+ Yp grown at 37°C. Comprehensive high-resolution tandem mass spectrometric analyses of lipid A extracted from Yp modified with either the C-1 or C-4′ phosphatase allowed for unambiguous structure assignment of monophosphorylated and diphosphorylated lipid A and distinction of isomeric bisphosphate and pyrophosphate forms. The prevalent aminoarabinose modification was determined to be exclusively attached to the lipid A disaccharide via a phospho-diester linkage at either or both the C-1 and C-4′ positions.     

Enzymatic Synthesis of Fructosyl Glycerol

ABSTRACT

The enzymatic synthesis of ß2-2' and ß2-1'-D- fructopyranosyl glycerol was carried out with levansucrase from Bacillus circulans or B.subtilis, using sucrose as fructosyl donor and glycerol. The specificity and efficiency of the enzyme was modified by controlling both the water and the total substrate concentrations. The products were purified by HPLC and analyzed by ¹H, ¹³C NMR and GC-MS.     

Synthesen von Heterocyclen, 111. Mitt.: Zur Umsetzung von Benzoylaceton und seinen Derivaten mit Malonylchlorid

Zusammenfassung Der Vorgang der thermischen Umlagerung des 4-Hydroxy-5-acetyl-6-phenyl-pyrons-(2) (1) zum 4-Hydroxy-5-benzoyl-6-methyl-pyron-(2) (4) wird an Hand weiterer Beispiele studiert und ferner der Einfluß der Substituenten am C-5 bzw. C-6 des Lactonringes untersucht.

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An investigation of more examples of the thermal rearrangement of 5-acetyl-4-hydroxy-6-phenyl-pyrone-(2) to 5-benzoyl-4-hydroxy-6-methyl-pyrone-(2) was carried out, it showed the influence of substituents at C-5 and C-6 of the lactone ring.

     

One new cycloartane triterpene glycoside from Beesia calthaefolia

One new cycloartane triterpene glycoside (1) was isolated from the whole plant of Beesia calthaefolia. Its structure was elucidated on the basis of extensive spectroscopic data analysis. Its inhibitory effect was measured by the classical pathway of the complement system, and compared with those of known related cycloartane glycosides 2 and 3, previously isolated by us from the same plant. Compounds 1 and 2 exhibited inhibitory activity of complement system with IC₅₀ of 395.3 and 214 μM, respectively. The results suggested that OH at C-12, C-18 and C-15 along with the polarity could affect the inhibitory activity.     

Molecular Mechanisms of Sweet Taste. V. Sucralose and Its Derivatives

Abstract

Chloro-deoxy-derivatives of sucrose, especially the intensely sweet 4, 1′,6′–trichloro-4,1′,6′-trideoxy-galacto-sucrose (Sucralose) and its derivatives, have been investigated in their peripheral interactions with a helical proteinaceous receptor model using computer graphics. In common with other high intensity sweeteners, they show multiple couplings with different side chains of the amino acid residues in the receptor protein.     

A Sucrose-Based Approach to Enantiomerically Pure Glycerol Derivatives

Abstract

Taking advantage of the same configuration present at C-5 and C-5′ in sucrose, 6,6′-diprotected sucrose derivatives were transformed into enantiomerically pure glycerol derivatives. This was achieved by oxidative ring cleavage of both the glucopyranosyl ring as well as the fructofuranosyl moiety followed by reduction of the resulting tetraaldehyde and subsequent per-O-protection of the resulting pentahydroxy compound. The obtained intermediate was hydrolysed under acidic conditions to furnish two equivalents of partially protected chiral glycerol derivative per molecule of starting material. The efficiencies of sodium metaperiodate and lead tetraacetate as oxidizing agents were compared and the side reactions observed in these procedures were investigated.     

NMR studies of 4(3H)-quinazolinones and 4(3H)-quinazolinethiones

Summary Unambiguous¹H and¹³C NMR assignments for 4(3H)-quinazolinones1–6 and their corresponding 4-thiones7–12 have been made. This resulted in the revision of the previous assignments for the two benzenoid carbons (C-5 and C-8) of quinazolinones1,2,4, and5. Thionation of the nucleophilic amides1–6 has been found to cause a distinct change in the¹³C chemical shift of particularly C-4, but also of those of C-4a, C-5, and C-8a. One-bond and several long range heteronuclear coupling constants for the compounds have also been measured.

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Kernresonanzspektroskopie von 4(3H)-Chinazolinonen und 4(3H)-Chinazolinthionen

Zusammenfassung Die¹H- und¹³C-NMR-Spektren der 4(3H)-Chinazolinone1–6 und ihrer entsprechenden 4-Thione7–12 wurden zugeordnet. Dabei zeigte sich, daß eine frühere Zuordnung der beiden benzoiden Kohlenstoffe (C-5 und C-8) der Chinazolinone1,2,4 und5 falsch war. Ersatz des Sauerstoffs durch Schwefel in den nukleophilen Amiden1–6 führt insbesondere für C-4, aber auch für C-4a, C-5 und C-8a zu einer deutlichen Änderung der chemischen Verschiebung. Heteronukleare Kopplungskonstanten über eine und über mehrere Bindungen wurden bestimmt.

     

A new malyngamide from the marine cyanobacterium Moorea producens

A new malyngamide (1) was isolated along with seven known compounds (2–8) from the marine cyanobacterium Moorea producens collected in Hawaii. Compound 1 represented the first reported malyngamide with a hydroxy moiety at C-7 of the characteristic fatty acid portion of the compound. Compound 1 showed cytotoxicity against L1210 cell line at an IC₅₀ value of 2.9 mM and lethal toxicity against the shrimp Palaemon paucidens at a LD₁₀₀ value of 33.3 mg/kg. The bioactivity of compound 1 was approximately 10–100 times weaker than those of isomalyngamides A and B (3, 4). These results indicated that the methoxy group at C-7 of the fatty acid section confers a degree of bioactivity in malyngamides.     

Antimalarial and cytotoxic activities of pregnene-type steroidal alkaloids from Holarrhena pubescens roots

The phytochemical investigation of an alkaloidal extract of Holarrhena pubescens roots led to the isolation and identification of a new pregnene-type alkaloid, mokluangin D (1), together with nine known steroidal alkaloids (2–10). The structure of the new metabolite was determined on the basis of spectroscopic analyses including 1D- and 2D-NMR spectroscopy and mass spectrometry. Compounds 3 and 4 showed potent antimalarial activity against Plasmodium falciparum K1 stain with IC₅₀ values of 1.2 and 2.0 μM, respectively, and showed weak cytotoxic activity against the NCI-H187 cell line with IC₅₀ values of 27.7 and 30.6 μM, respectively. The substituent groups at C-3 and the carbonyl group at C-18 are important for the activity against the P. falciparum K1 stain.     

刚性双(三氮唑)和羧酸混合配体构建的两种金属有机骨架材料及其在CO2环加成反应中的催化性质

通过酸碱混合配体策略合成了 2 例含刚性双三氮唑配体的金属有机骨架(MOF)材料：{[Zn₂(L)(TP)₂(H₂O)·H₂O]}_n (1)和[Zn(L)(HTMA)]_n (2),其中L=4,4''-(3,3''-dimethyl-(1,1''-biphenyl)-4,4''-diyl)bis(4H-1,2,4-triazole),H₂TP=对苯二甲酸,H₃TMA=1,3,5-均苯三甲酸。用单晶 X 射线衍射表征其结构。结构分析表明,MOF 1显示出 3,6-双节点的二维结构,其拓扑符号为(4²·6)₂(4⁸·6⁶·8),MOF 2呈现为经典的 sql二维拓扑结构。在温和条件下,2对 CO₂与环氧化物的环加成反应具有优异的催化活性,且重复使用至少3次后仍然保持其催化性能。     

Genkwalathins A and B,new lathyrane-type diterpenes from Daphne genkwa

Screening for new natural anti-neuroinflammatory compounds was performed with the traditional folk medicine Genkwa Flos, which potently inhibited nitric oxide (NO) production by LPS-activated microglial BV-2 cells. Two new lathyrane-type diterpenes, genkwalathins A (1) and B (2), and 14 known daphnane-type diterpenes (3–16) were isolated. The lathyrane-type diterpenes were isolated for the first time from the Thymelaeaceae family in this study. Compounds 1 and 2 moderately inhibited LPS-induced NO production in BV-2 cells without affecting cell viability, while six daphnane-type diterpenes (3, 4, 6, 7, 9 and 10) potently reduced NO production with IC₅₀ values less than 1 μM, although they did display weak cytotoxicity. A structure–activity relationship study on the daphnane-type diterpenes indicated that the stereochemistry at C-19, the benzoate group at C-20, and the epoxide moiety could be important for their anti-neuroinflammatory effects.