Application of the superarmed glycosyl donor to chemoselective oligosaccharide synthesis

Recently, we discovered a novel method for "superarming" glycosyl donors. Herein, this concept has been exemplified in one-pot oligosaccharide syntheses, whereby the superarmed glycosyl donor was chemoselectively activated over traditional "armed" and disarmed glycosyl acceptors. Direct side-by-side comparison of the reactivities of the classic armed and superarmed glycosyl donors further validates the credibility of the novel concept.     

底物控制策略快速装配低聚糖

综述了用底物控制策略快速装配低聚糖的新进展     

Glycosidation of thioglycosides in the presence of bromine: mechanism, reactivity, and stereoselectivity

Elaborating on previous studies by Lemieux for highly reactive "armed" bromides, we discovered that β-bromide of the superdisarmed (2-O-benzyl-3,4,6-tri-O-benzoyl) series can be directly obtained from the thioglycoside precursor. When this bromide is glycosidated, α-glycosides form exclusively; however, the yields of such transformations may be low due to the competing anomerization into α-bromide that is totally unreactive under the established reaction conditions.     

Preparation, properties, and applications of n-pentenyl arabinofuranosyl donors

[reaction: see text] The development of n-pentenyl furanosyl donors has been tested using arabinose as a model. The readily prepared ortho ester (NPOE) is converted into disarmed (NPG(AC)) and thence armed (NPG(ALK)) n-pentenyl arabinofuranosides. The reactivities of these furanosyl donors and pyranosyl counterparts have been assessed by allowing pairs of both to compete for an acceptor. For the NPOE and armed (NPG(ALK)) pairs, coupling products were obtained from donors, whereas for the disarmed (NPG(AC)) pair, only the arabinofurano coupled product was obtained. To probe their synthetic utility, the NPOE was shown to be the only precursor needed to prepare an alpha-1,5-linked arabinan segment of the complex lipoarabinomannan cell wall array of Mycobacterium tuberculosis.     

Relevance of the glycosyl donor to the regioselectivity of glycosidation of primary-secondary diol acceptors and application of these ideas to in situ three-component double differential glycosidation

[reaction: see text] Three pairs of primary-secondary diol acceptors have been exposed to armed, disarmed, and n-pentenyl ortho ester glycosyl donors in glycosidation reactions. It is shown that the regioselectivity of those glycosylations is greatly influenced by the armed, disarmed, or ortho ester nature of the glycosyl donors. The selectivities observed have been used to devise efficient in situ three-component glycosylations involving two donors and one acceptor.     

O,O-dimethylthiophosphonosulfenyl bromide-silver triflate: a new powerful promoter system for the preactivation of thioglycosides

O,O-Dimethylthiophosphonosulfenyl bromide (DMTPSB) in combination with silver triflate provides a powerful thiophilic promoter system. Both "armed" and "disarmed" thioglycoside glycosyl donors can be activated to form glycosidic linkages efficiently by the pre-activation protocol. The usefulness of this new promoter is illustrated by a successful iterative one-pot oligosaccharide assembly.     

Convergent synthesis of a pentasaccharide repeating unit corresponding to the cell wall O-antigen of Salmonella enterica O44

A convergent synthetic strategy has been developed for the synthesis of a pentasaccharide fragment corresponding to the O-antigen of Salmonella enterica O44 strain. An intermediate tetrasaccharide derivative was prepared by a [2+2] block glycosylation of two disaccharide derivatives. The p-methoxybenzyl (PMB) group has been used as the in situ temporary protecting group minimizing the number of functional group manipulation steps. The application of the armed–disarmed glycosylation concept reduced the number of steps in the synthetic strategy. The glycosylation steps were highly stereoselective and high yielding.     

Ph2SO/Tf2O: a powerful promotor system in chemoselective glycosylations using thioglycosides

Diphenylsulfoxide in combination with triflic anhydride provides a very potent thiophilic glycosylation promotor system, capable of activating disarmed thioglycosides. The usefulness of this novel thiophilic activator is illustrated in a successful chemoselective glycosylation sequence in which the donor thioglycoside in the first condensation step may be either armed or disarmed. [reaction: see text]     

1-Benzenesulfinyl piperidine/trifluoromethanesulfonic anhydride: a potent combination of shelf-stable reagents for the low-temperature conversion of thioglycosides to glycosyl triflates and for the formation of diverse glycosidic linkages

The combination of 1-benzenesulfinyl piperidine (BSP) and trifluoromethanesulfonic anhydride (Tf(2)O) forms a new, powerful, metal-free thiophile that can readily activate both armed and disarmed thioglycosides, via glycosyl triflates, in a matter of minutes at -60 degrees C in dichloromethane, in the presence of 2,4,6-tri-tert-butylpyrimidine (TTBP). The glycosyl triflates are rapidly and cleanly converted to glycosides, upon treatment with alcohols, in good yield and selectivity.     

One pot/two donors/one diol give one differentiated trisaccharide: powerful evidence for reciprocal donor-acceptor selectivity (RDAS)

Three component, one-pot reactions involving equimolar amounts of the acceptor diol and both armed and disarmed donors presented simultaneously, produce a single double-differential glycosidation product; this phenomenon provides evidence for Reciprocal Donor Acceptor Selectivity (RDAS).     

Additive‐Free Gold(III)‐Catalyzed Stereoselective Synthesis of 2‐Deoxyglycosides Using Phenylpropiolate Glycosides as Donors

Stereoselective synthesis of deoxyglycosides has been achieved from benchtop stable and easily synthesizable deoxy‐phenylpropiolate glycosides (D‐PPGs) using gold(III) salt as catalyst under external additive‐free conditions. Under a simple catalytic system, D‐PPGs reacted with a variety of sugar and non‐sugar acceptors to produce majorly α‐stereoselective O/N‐deoxyglycosides in good to excellent yields and regenerate easily separable and reusable phenylpropiolic acid. Deoxy‐PPGs containing armed and disarmed groups survived well under the optimized reaction conditions. In addition, the orthogonal nature of D‐PPGs was showcased, and 1,1′‐linked trehalose‐type sugar was also synthesized.     

Glycosidation with a disarmed glycosyl iodide: promotion and scope

[reaction: see text] Glucuronyl iodide 1 has been studied in detail as a "disarmed" glycosyl donor. In a model reaction, using N-iodosuccinimide (NIS) as a promoter and 2-phenylethanol as acceptor, best results were obtained using NIS with I(2), followed by trimethylsilyltrifluoromethanesulfonate (TMSOTf). When a series of primary and secondary alcohols was glycosylated using these conditions, yields of 60-83% of beta-glucuronides were obtained. Various "nonheavy" metal salts also effectively catalyzed the model reaction but led to significant amounts of alpha-product with less reactive secondary alcohols.     

Microwave-assisted saccharide coupling with n-pentenyl glycosyl donors

n-Pentenyl glycosides, armed and disarmed, and n-pentenyl orthoesters couple with acceptors, hindered and unhindered, within 25 min under microwave activation. The reaction takes place in acetonitrile under neutral conditions with N-iodosuccinimide as promotor, which are therefore ideal for use with reactants bearing acid-labile protecting groups.     

5-氟脲嘧啶的β-D-半乳吡喃糖苷的合成

5-氟脲嘧及其衍生物是目前临床上广泛使用的抗代谢类抗癌药物, 主要适用于消化道癌、乳腺癌、肺癌等, 但具有一定的毒性, 主要表现为骨髓抑制和胃肠道反应。我们以Koenigs-Knorr法和相转催化法合成了5-氟脲嘧啶的两种类型(-N型, -O型)的半乳吡喃糖苷。这些糖苷类化合物在体内糖苷的作用下, 有可能缓慢地分解释放出5-氟脲嘧啶, 降低其毒性, 提高抑瘤效果。     

Observations on the activation of methyl thioglycosides by iodine and its interhalogen compounds,

Treatment of ‘armed’ methyl thiogalactosides with iodine in the absence of an acceptor alcohol results in thioglycoside epimerisation, whereas there is no effect on the corresponding ‘disarmed’ methyl thioglycosides. In contrast, iodine–hexamethyldisilane (which generates iodotrimethylsilane in situ) brings about epimerisation of ‘disarmed’ thioglycosides, ultimately giving rise to the corresponding α-glycosyl iodides on extended exposure. Cross-over experiments show the former iodine-promoted epimerisation process to be intermolecular, whereas the latter iodine–hexamethyldisilane-promoted epimerisation is intramolecular. Treatment of the same methyl thiogalactosides with iodine monobromide gives rise to the thermodynamically favoured α-glycosyl bromides, whereas reaction with iodine monochloride initially gives the kinetic β-glycosyl chlorides, which slowly epimerise to the thermodynamic α-linked products. Differences in the outcome of thioglycoside activation by I–I, I–Br and I–Cl suggest there may be scope for influencing the stereochemical course of thioglycoside-based glycosylation reactions through careful choice of promoter.     

Methyl 2-azido-3-O-benzyl-2-deoxy-α-D-mamnofuranoside as a divergent intermediate for the synthesis of polyhydroxylated piperidines and pyrrolidines: synthesis of 2,5-dideoxy-2,5-imino-D-mannitol [2R,5R-dihydroxymethyl-3R,4R-dihydroxypyrrolidine]

The synthesis of methyl 2-azido-3-O-benzyl-2-deoxy-α-D-mannofuranoside (1) from D-glucose is reported; the conversions of (1) into derivatives of methyl 3-O-benzyl-2,6-dideoxy-2,6-imino-α-D-mannofuranoside (as precursors for the synthesis of polyhydroxylated piperidines) and into the hydroxylated pyrrrolidine, 2,5-dideoxy-2,5-imino-D-mannitol [2R,5R-dihydroxymethyl-3R,4R-dihydroxypyrrolidine] are described.     

新型海参硫酸软骨素葡萄糖受体及葡萄糖醛酸受体的高效合成

以D-葡萄糖为起始原料,经9步反应合成了2-O-苄基-3-O-烯丙基-1-O-对甲氧基苯基α-D-葡萄糖(9);将9的6-位伯羟基经叔丁基二苯基硅烷基(TBDPS)保护,首次合成了正交保护的新型葡萄糖受体2-O-苄基-3-O-烯丙基6-O-叔丁基二苯基硅烷基1-O-对甲氧基苯基α-D-葡萄糖(Ⅱ),总收率28.2%;将9的6-位伯羟基氧化糖醛酸化后,再经甲酯化,以25.0%的总收率首次合成了新型葡萄糖醛酸受体2-O-苄基-3-O-烯丙基-1-O-对甲氧基苯基α-D-葡萄糖醛酸甲酯(Ⅲ),化合物结构经¹H NMR,¹³C NMR, IR和HR-MS(ESI)表征。     

Gold-catalyzed glycosidations: unusual cleavage of the interglycosidic bond while studying the armed/disarmed effect of propargyl glycosides

Armed/disarmed effect of propargyl glycosides in the presence of AuBr₃ is studied. Observed that oxophilic AuBr₃ cleaves interglycosidic bond of an armed disaccharide resulting in the formation of a disaccharide and a 1,6-anhydro sugar. Trisaccharides were obtained after fine tuning the reactivity of the glycosyl donor with different protecting groups.     

Carbohydrates as nucleophiles in conjugate addition for preparation of muramic acid analogues

Benzyl 2-acetamido-6-O-benzyl-3-O-[(S)-1-carboxy-isopropyl]-- -glucopyranoside (15) was synthesized stereoselectively by conjugate addition reaction, starting irom benzyl 2-acetamido-6-O-benzyl-2-deoxy--D-glucopyranoside (9) and crotonic acid ethyl ester under phase transfer conditions. The dipeptide L-Ala-D-Glu(OMe)OMe was coupled to 15 to give compuond 25 an analogue of the adjuvant active muramyl dipeptide (MDP)     

Synthesis of macrolide antibiotics Communication 3. Synthesis of the C9-C13 fragments of oleandonolide and erythronolide B

Conclusions Using Cp₂Zr(H)Cl, 1,6-anhydro-2-desoxy-2-C-methyl-3-O-benzyl-4-methylene--D-xylohexapyranose has been reduced with a high degree of stereospecificity to 1,6-anhydro-2,4-didesoxy-2,4-di-C-methyl-3-Obenzyl--D-galactopyranose, which was then converted into the C⁹-C¹³ fragments of erythronolide Band oleandonolide.Short communication [1]; previous communication [2].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2568–2572, November, 1982.