Total Synthesis of Tricolorin A

NODA N., KOBAYASHI H., MIYAHARA K., KAWASAKI T.

Contrary to the work of Khanna and Gupta [Phytochemistry, 6, 735 (1967)], alkaline hydrolysis of the glycoside fraction obtained from the seeds of Ipomoea muricata (L) JACQ. (Convolvulaceae) gave three glycosidic acids, muricatic acids A (5), B (6) and C (trace), together with isobutyric, 2S-methylbutyric and (2R, 3R)-nilic (3-hydroxy-2-methylbutyric) acids. Muricatic acids A and B were characterized 11R-jalapinolic acid 11-O-β-D-fucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-β-D-quinovopyranosyl-(1→2)-β-D-quinovopyranoside and 11R-jalapinolic acid 11-O-β-D-quinovopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-β-D-quinovopyranosyl-(1→2)-β-D-quinovopyranoside, respectively, on the basis of chemical and spectroscopic data.The similarity of the component organic and glycosidic acids to those of resin glycoside from I. orizabensis suggests the glycoside fraction to be a mixture of so-called resin glycosides.

Erbing B., Lindberg B., Lindberg B., Svensson S., Taticchi A., Anthonsen T.

Bah M., Pereda-Miranda R.

Extensive NMR and FAB-MS studies have led to the characterization of tricolorins A-E, major phytogrowth inhibitors present in the allelopathic glycoresin of Ipomoea tricolor Cav. (Convolvulaceae). The purification of these tetraglycosides was successfully achieved by an amino bonded-phase HPLC methodology. Tricolorins B-D differed from the previously reported macrocycle structure of tricolorin A in the site of lactonization as well as in the type and location of short-chain acids ester-linked at the oligosaccharide core (tricoloric acid A). The structure of tricolorin E was based on a new linear tetraglycoside of jalapinolic acid (tricoloric acid B).

Larson D.P., Heathcock C.H.

Jiang Z., Geyer A., Schmidt R.R.

García Fernández J., Ortiz Mellet C., Moreno Marín A., Fuentes J.

Takeo K., Nagayoshi K., Nishimura K., Kitamura S.

Abstract The 8-methoxycarbonyloctyl β-glycosides of the trisaccharides O-β-d-Glcp-(1 → 6)- O-β-d-Glcp-(1 → 3)-d-Glcp and O-β-d-Glcp-(1 → 3)-O-[β-d -Glcp-(1 → 6)]-d-Glcp and of the tetrasaccharide O-β-d-Glcp-(1 → 3)-O-[β-d-Glcp-(1 → 6)]-O-β-d-Glcp-(1 → 3)-d-Glcp, corresponding to the fragments of schizophyllan, have been synthesized by using mono- to tetrasaccharide 1-thioglycosides as glycosyl donors, each bearing a participating benzoyl group in the 2-position, and N-iodosuccinimide and silver triflate as promoter. Saponification of the tri- and tetrasaccharide β-glycosides, followed by attachment to bovine serum albumin of the resulting sugar derivatives having a carboxyl group at the aglycon terminal, provided neoglycoproteins for immunological studies of the polysaccharide.

Jiang Z., Schmidt R.R.

3-O-Benzyl-protected quinovose 6 was transformed into 1,2-O-unprotected derivative 9 which on treatment with TBS-Cl in the presence of a base gave selectively 2-O-unprotected glycosyl acceptor 10. Similarly, 3-O-allyl-protected quinovose 11 was transformed into 1,2-O-unprotected derivative 14. 1,2-O-Acetylation of 14, selective removal of the 1-O-acetyl group with hydrazinium acetate, and subsequent treatment with trichloroacetonitrile in the presence of DBU furnished the versatile 2-O-acetyl-3-O-allyl-protected quinovosyl donor 17. Reaction of donor 17 with acceptor 10 in the presence of TMSOTf as the catalyst gave disaccharide 19. Treatment of 19 with NaOMe/MeOH provided 2b-O-unprotected derivative 20 which gave with rhamnosyl donor 18 in the presence of TMSOTf as the catalyst trisaccharide 21. 3b-O-Deallylation of 21 and subsequent reaction with donor 17, again in the presence of TMSOTf as the catalyst, gave target tetrasaccharide 2. Removal of all O-protective groups furnished D-Quis(13)[L-Rhaα(12)]D-Quis(12)D-Qui (3), the tetrasaccharide moiety of calonyctin A.

Zuurmond H.M., Van Der Meer P.H., Van Der Klein P.A., Van Der Marel G.A., Van Boom J.H.

Abstract Fully benzylated or benzoylated phenyl selenoglycosides can be activated by the promoters iodonium di-sym-collidine perchlorate (IDCP) or N-iodosuccinimide and catalytic triflic acid (NIS/TfOH). The potential of the iodonium ion-mediated glycosylations with phenyl selenoglycosides is illustrated in the chemoselective synthesis of 1,2-cis-and 1,2-trans linked disaccharides.

Kováč P.

Methyl O -(2,4-di- O -benzoyl-3- O -bromoacetyl-α- l -rhamnopyranosyl)-(1 → 3)-2,4-di- O -benzoyl-α- l -rhamnopyranoside was treated with dichloromethyl methyl ether and ZnCl 2 to give O -(2,4-di- O -benzoyl-3- O -bromoacetyl-α- l -rhamnopyranosyl)-(1 → 3)-2,4-di- O -benzoyl-α- l -rhamnopyranosyl chloride. Similar treatment of methyl O -(3,4-,6-tri- O -acetyl-2-azido-2-deoxy-α- d -glycopyranosyl)-(1 → →3)-2,4-di- O -benzoyl-α- l -rhamnopyranoside ( 13 ) gave crystalline O -(3,4,6-tri- O -acetyl-2-azido-2-deoxy-α- d -glucopyranosyl)-(1 → 3)-2,4-di- O -benzoyl-α- l -rhamnopyranosyl chloride ( 14 ), which was also obtained by treatment of methyl O -(3,4,6-tri- O -acetyl-2-azido-2-deoxoy-α- d -glucopyranosyl)-(1 → 3)-2,4-di- O -benzoyl-1-thio-α, l -rhamnopyranoside ( 12 ) with chlorine. In contrast to the conversion 12 → 14 , which was stereospecific, the reaction of methyl O -(3,4,6-tri- O -acetyl-2-azido-2-deoxy-α- d -glucopyranosyl)-(1 → 3)-( O -2,4-di- O -benzoyl-α- l -rhamnopyranosyl)-(1 → 3)-2,4-di- O -benzoyl-1-thio-α- l -rhamnopyranoside with chlorine gave a mixture of the corresponding α-( 16 ) and β-( 17 ) glycosyl chlorides. Condensation of the mixed chlorides 16 and 17 with 1,3,4,6-tetra- O -acetyl-α- d -galactopyranose, followed by reduction-acetylation of the product, gave a fully protected derivative of the tetrasaccharide α- d -Glc p NAc-(1 → 3)-α- l -Rha p -(1 → 3)-α- l -Rha p -(1 → 2)-α- d -Gal p .

Pereda-Miranda R., Mata R., Anaya A.L., Wickramaratne D.B., Pezzuto J.M., Kinghorn A.D.

The allelopathic potential of Ipomoea tricolor (Convolvulaceae), used in Mexican traditional agriculture as a weed controller, has been demonstrated by measuring the inhibitory activity of organic extracts on seedling growth of Amaranthus leucocarpus and Echinochloa crus-galli. Bioactivity-directed fractionation of the active CHCl3 extract led to the isolation of the allelopathic principle, which turned out to be a mixture of the so-called "resin glycosides" of convolvulaceous plants. The structure of tricolorin A, the major phytogrowth inhibitor present in the active fraction, was elucidated as (11S)-hydroxyhexadecanoic acid 11-O-alpha-L-rhamnopyranosyl-(1-->3)-O-alpha-L-[2-O-(2S-methylbutyryl)-4 -O- (2S-methylbutyryl)] rhamnopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->2)-beta-D-fucopyran oside- (1,3"-lactone)[1], based on chemical methods and spectral analysis including 1H-1H COSY, 1H-13CHETCOR, long range 1H-13C COLOC, and selective INEPT experiments. Bioassays showed that radicle elongation of the two weed seedlings tested was inhibited by tricolorin A [1] with IC50 values ranging from 12 to 37 microM. Staphylococcus aureus was sensitive to compound 1 with an MIC value of 1.8 micrograms/ml. Significant cytotoxic activity against cultured P-388 and human breast cancer cells (ED50 2.2 micrograms/ml) was demonstrated for compound 1, and it also inhibited phorbol 12,13-dibutyrate binding using calf brain homogenate as a source of protein kinase C (IC50 43 microM).

Lerner L.M.

Zegelaar-Jaarsveld K., van der Marel G.A., van Boom J.H.

The spacer containing trimer 4-(aminoethyl)phenyl 2,4-di-O-Me-3-O-[2-O-methyl-3-O-(4-O-acetyl-2-O-methyl-α- l -fucopyranosyl)-α- l -rhamnopyranosyl]-α- l - rhamnopyranoside (2) was prepared by stepwise extension of 4-[2-(benzyloxycarbonyl-amino)ethyl]phenyl 2,4-di-O-methyl-α- l -rhamnopyranoside (19) with properly protected ethyl thioglycosides of l -rhamnose 8 and l -fucose 12 or 16 using iodonium ions as promotors. The resulting trimers 22 or 23 were deblocked in two steps to give homogeneous 2. Alternatively, fully protected trimer 22 was assembled by iodonium ion assisted condensation of the phenyl 1-thio-α- l -rhamnopyranoside 29 with 12 followed by extension of dimer 31 with 19.

Veeneman G.H., van Boom J.H.

Chemospecific glycosidation of partially-benzoylated thioglycosides (“disarmed” acceptors) with perbenzylated thioglycosides (“armed” donors) can be realized in the presence of the promotor iodonium dicollidine perchlorate. The reaction results predominantly in the formation of α-linked saccharides and is compatible with the use of various protecting groups.

Konradsson P., Udodong U.E., Fraser-Reid B.

N-Iodosuccinimide/trifluoromethanesulfonic acid, which had been shown to promote the solvolysis of disarmed n-pentenyl glycosides, has been found to induce the same reactivity with disarmed thioglycosides as substrates. N-Iodosuccinimide/trifloromethanesulfonic acid, which had been showed to promoete the solvolysis of disarmed n-pentenyl glycosides, has been found to induce the same reactivity with disarmed thioglycosides as substrates. NIS/AgOTf or NIS/Et 3 SiOTf also proves to be an excellent source of iodonium ion

Mountanea O.G., Mantzourani C., Gkikas D., Politis P.K., Kokotos G.

Hydroxy fatty acids (HFAs) constitute a class of lipids, distinguished by the presence of a hydroxyl on a long aliphatic chain. This study aims to expand our insights into HFA bioactivities, while also introducing new methods for asymmetrically synthesizing unsaturated and saturated HFAs. Simultaneously, a procedure previously established by us was adapted to generate new HFA regioisomers. An organocatalytic step was employed for the synthesis of chiral terminal epoxides, which either by alkynylation or by Grignard reagents resulted in unsaturated or saturated chiral secondary alcohols and, ultimately, HFAs. 7-(S)-Hydroxyoleic acid (7SHOA), 7-(S)-hydroxypalmitoleic acid (7SHPOA) and 7-(R)- and (S)-hydroxymargaric acids (7HMAs) were synthesized for the first time and, together with regioisomers of (R)- and (S)-hydroxypalmitic acids (HPAs) and hydroxystearic acids (HSAs), whose biological activity has not been tested so far, were studied for their antiproliferative activities. The unsaturation of the long chain, as well as an odd-numbered (C17) fatty acid chain, led to reduced activity, while the new 6-(S)-HPA regioisomer was identified as exhibiting potent antiproliferative activity in A549 cells. 6SHPA induced acetylation of histone 3 in A549 cells, without affecting acetylated α-tubulin levels, suggesting the selective inhibition of histone deacetylase (HDAC) class I enzymes, and was found to inhibit signal transducer and activator of transcription 3 (STAT3) expression.

Wang W., Li Y., He Y., Jiang X., Yi Y., Zhang X., Zhang S., Chen G., Yang M., Luo J., Fan B.

Resin glycosides, mainly distributed in plants of the family Convolvulaceae, are a class of novel and complex glycolipids. Their structural complexity and significant biological activities have received much attention from synthetic chemists, and a number of interesting resin glycosides have been synthesized. The synthesized resin glycosides and their analogues not only helped in structural verification, structural modification, and further biological activity exploration but also provided enlightenment for the synthesis of glycoside compounds. Herein, the present review summarizes the application of various efforts toward the synthesis of resin glycosides in the last decade.

Brito-Arias M.

When a monosaccharide (or sugar fragment of any size) is condensed with either an aliphatic or aromatic alcohol, or another sugar moiety through an oxygen, a glycoside bond is formed. General examples of O-glycosides-glycosides are shown in Scheme 2.1.

Sun J., Fang J., Xiao X., Cai L., Zhao X., Zeng J., Wan Q.

The total synthesis of tricolorin A was achieved with high efficiency based on interrupted Pummerer reaction-mediated (IPRm) glycosylation and one-pot relay glycosylation.

Fang J., Zeng J., Sun J., Zhang S., Xiao X., Lu Z., Meng L., Wan Q.

Murucoidins IV and V, two bioactive resin glycosides with complex yet similar structures isolated from the morning glory family, were synthesized in a convergent manner. All of the glycosylations in these syntheses including the key [3 + 2] coupling were achieved by our recently developed interrupted Pummerer reaction mediated (IPRm) glycosylations. The broad functional group compatibility of IPRm glycosylation allowed us to employ a latent-active concept and a single-pot transient protection-glycosylation-deprotection strategy which significantly improved the global synthetic efficiency.

Jana S., Sarpe V.A., Kulkarni S.S.

Fungal glycolipids emmyguyacins A and B inhibit the pH-dependent conformational change of hemaglutinin A during replication of the Influenza virus. Herein, we report the first total synthesis and structure confirmation of emmyguyacins A and B. Our efficient route, which involves regioselective functionalization of trehalose, allows rapid access to adequate amounts of chemically pure emmyguyacin analogues including the desoxylate derivatives for SAR studies.

Kulkarni S.S., Wang C., Sabbavarapu N.M., Podilapu A.R., Liao P., Hung S.

Carbohydrates, which are ubiquitously distributed throughout the three domains of life, play significant roles in a variety of vital biological processes. Access to unique and homogeneous carbohydrate materials is important to understand their physical properties, biological functions, and disease-related features. It is difficult to isolate carbohydrates in acceptable purity and amounts from natural sources. Therefore, complex saccharides with well-defined structures are often most conviently accessed through chemical syntheses. Two major hurdles, regioselective protection and stereoselective glycosylation, are faced by carbohydrate chemists in synthesizing these highly complicated molecules. Over the past few years, there has been a radical change in tackling these problems and speeding up the synthesis of oligosaccharides. This is largely due to the development of one-pot protection, one-pot glycosylation, and one-pot protection-glycosylation protocols and streamlined approaches to orthogonally protected building blocks, including those from rare sugars, that can be used in glycan coupling. In addition, new automated strategies for oligosaccharide syntheses have been reported not only for program-controlled assembly on solid support but also by the stepwise glycosylation in solution phase. As a result, various sugar molecules with highly complex, large structures could be successfully synthesized. To summarize these recent advances, this review describes the methodologies for one-pot protection and their one-pot glycosylation into the complex glycans and the chronological developments associated with automated syntheses of oligosaccharides.

Liu Y., Zeng J., Sun J., Cai L., Zhao Y., Fang J., Hu B., Shu P., Meng L., Wan Q.

An efficient deprotection of the ketal and acetal type protecting groups has been achieved with Brønsted acid as a catalyst and 1,4-dithiothreitol as a ketal or acetal exchange reagent.

Rodriguez J., O'Neill S., Walczak M.A.

Conformationally restricted natural products containing hydrocarbon tethers attached to an oligosaccharide chain display intriguing structural and biological properties.

Zong G., Shi W.Q.

As a unique family of resin glycosides, ipomoeassins exhibit exceptionally high potency against cancer cell growth with a novel unknown mode of action. This account describes the development of a more efficient synthetic route for scalable assembly of ipomoeassin F, a flagship congener of the family. The new synthesis highlights a series of highly regioselective transformations, including α configuration-controlled allyloxycarbonylation of a glucose diol, TBS silylation of a fucose triol, and stereospecific β glycosylation of a fucose diol. Immediately after the completion of the synthesis, we also embarked on systematic exploration of structure–activity relationship for ipomoeassin F and acquired a great amount of firsthand information on its pharmacophore. The new knowledge on organic synthesis and medicinal chemistry studies will expand applications of the ipomoeassins to more areas of biomedical research in the future.

Hu Y., Yu K., Shi L., Liu L., Sui J., Liu D., Xiong B., Sun J.

A novel alkyne-activation-based glycosylation protocol using o-(p-methoxyphenylethynyl)phenyl (MPEP) glycoside was established. The glycosyl MPEP donors were shelf-stable and could be prepared efficiently via Sonogashira reaction from the corresponding o-iodophenyl (IP) glycosides. The outstanding stability of IP glycosides as well as their efficient transformations to MPEP glycosides dramatically facilitates the syntheses of MPEP glycosyl donors and IP glycosyl acceptors. Furthermore, they make the MPEP glycosylation protocol applicable to the latent-active oligosaccharide and glycoconjugate synthetic strategy, with IP glycosides as the latent form and MPEP glycosides as the active form, as illustrated by the highly efficient fabrication of Streptococcus pneumoniae type 3 trisaccharide. The phenolic glycoside nature of MPEP glycosides bestows on the new glycosyl donors enhanced stability compared to their thioglycoside counterparts toward activation conditions applied for glycosyl trichloroacetimidate (TCAI) and o-alkynylbenzoate (ABz) donor. Thus, MPEPs can also be utilized in the selective one-pot glycosylation strategy, as exemplified by the syntheses of oligosaccharides via successive glycosylations with glycosyl TCAI, ABz, and EPMP as donors. Despite sharing identical promotion conditions with thioglycoside donors, the odor-free starting material (IP), the stable departure structure of the leaving group (3-iodobenzofuran), and the decreased nucleophilicity of the o-MPEP glycoside help to eliminate the three major shortcomings of the thioglycoside donors (unpleasant odor of starting material, detrimental interference of the cleaved leaving group, and aglycon intra- or intermolecular migration) while maintaining the prominent features of the thioglycoside methodology, including the broad substrate scopes, the mild promotion conditions, the stability of glycosyl donors, and the versatile applications in existing glycoside synthesis strategies. Based on the experimental results, a mechanism for MPEP activation was proposed, which was supported by systematic mechanistic investigations, including trapping of active intermediates, design of a vital disarmed rhamnosyl donor, and isolation and characterization of the departure species of the leaving group.

Yang B., Yoshida K., Huang X.

One-pot oligosaccharide synthesis refers to approaches by which one glycosyl building block is subjected to successive chemical reactions in the same flask without the need to purify the intermediates. Traditionally, oligosaccharide synthesis is carried out in a stepwise fashion. Upon the successful formation of a glycosidic linkage, further elongation of the glycan chain requires that the newly formed oligosaccharide is either deprotected to generate a new glycosyl acceptor or transformed into a new glycosyl donor by modifying its aglycone. Although many complex oligosaccharides have been assembled in this manner, the stepwise approach is tedious and time consuming due to the need for multiple protecting group adjustment and aglycone leaving group manipulation on oligosaccharide intermediates. In order to improve the overall synthetic efficiency, one-pot strategies have been designed. It can potentially improve the speed of the overall synthetic operations and increase reaction yields by reducing product loss due to purification.

Brito-Arias M.

When a monosaccharide (or a sugar fragment of any size) is condensed with either an aliphatic or aromatic alcohol, or another sugar moiety through oxygen, a glycoside bond is formed. General examples of -glycosides are shown in Scheme 2.1.

Moya-López J.F., Elhalem E., Recio R., Álvarez E., Fernández I., Khiar N.

Theexo-anomeric effect paves the way for the synthesis of the usually less favoredRS-β-sulfinyl glycoside as a single diastereoisomer.