An enantiospecific synthesis of a crinipellin

An enantiospecific synthesis of a crinipellin has been accomplished, starting from the readily available (S)-campholenaldehyde employing two intramolecular rhodium carbenoid CH insertions and an intramolecular Michael addition reaction as key steps.

Enantiospecific total synthesis of 15-hydroxy-5-(methoxymethoxy)crinipellin-9-one

Enantiospecific total synthesis of the crinipellin mentioned in the title was accomplished. In the present synthesis cyclopentane ring in campholenaldehyde was identified as the B-ring, two intramolecular rhodium carbenoid CH insertion reactions were employed for the construction of the A and C rings, and an intramolecular Michael addition reaction was utilized for the construction of the D-ring of crinipellin. (C) 2012 Elsevier Ltd. All rights reserved.

Deoxythiosugar Derivatives with Furano, Pyrano, and Septano Motifs from L-Gulono-1,4-lactone and D-Glycero-D-gulo-heptono-1,4-lactone

A short synthesis of thiosugar derivatives mimicking furanose, pyranose, and septanose structures has been achieved starting from L-gulono-1,4-lactone and D-glucoheptono-1,4-lactone. Different strategies used in the synthesis are: (1) a nucleophilic displacement and Michael addition; (2) epoxide ring opening and Michael addition; (3) epoxide ring opening and nucleophilic displacement process; and (4) double nucleophilic displacement. All of these reactions used benzyltriethylammonium tetrathiomolybdate, (BnEt3N)(2)MoS4 as the sulfur-transfer reagent.

Progress towards the total synthesis of a spermine-conjugated dynemicin analog

Progress towards the synthesis of the spermine-conjugated Dynemicin analog 4 is described. The synthetic route starts with the Michael addition of menthyl acetoacetate to trans-ethyl crotonate followed by a Dieckman condensation to form the cyclohexanedione 14 which, through a series of chemical reactions, is transformed into the quinone imine 6. Key features in the route include the Suzuki coupling reaction of the aryl boronic acid 11 and the enol triflate 12, thermal deprotection/internal amidation of the biaryl 19, cis addition of the (Z)-enediyne 33 to the quinoline 25, intramolecular acetylide addition to a carbonyl within the ketone 29, and an addition/elimination of the cyanophthalide to the quinone imine 6 to form the anthraquinone 36 utilizing the Kraus and Sugimoto methodology.

Synthesis and stereochemical assignments of diastereomeric Ni(II) complexes of glycine Schiff base with (R)-2-(N-{2-[N-alkyl-N-(1-phenylethyl)-amino]acetyl}amino) benzophenone; a case of configurationally stable stereogenic nitrogen

A family of chiral ligands derived from alpha-phenylethylamine and 2-aminobenzophenone were prepared by alkylation of the nitrogen atom. Upon reaction with glycine and a Ni(II) salt, these ligands were transformed into diastereomeric complexes, as a result of the configurational stability of the stereogenic nitrogen atom. Different diastereomeric ratios were observed depending on the substituent R introduced in the starting ligand, and stereochemical assignments were based on X-ray analysis, along with NMR studies and optical rotation measurements.

具有环氧化酶-2选择性抑制活性的多取代蒽醌的合成

1-甲基-2-甲氧羰基-3, 6, 8-三羟基-7-甲氧基蒽醌是从唐菖蒲干球茎中分离到的具有环氧化酶-2选择性抑制活性的多取代蒽醌类化合物。本文试图合成该化合物，实现了其类似物的合成，同时发现了几个未见报道的反应。 1．通过Diels-Alder 反应合成了关键中间体——3-甲基-5-羟基-1, 2, 4-苯三甲酸三甲酯，1-COOMe选择性水解产物与1, 2, 3-三甲氧基苯进行分子间Friedel-Crafts反应的产物再进行分子内Friedel-Crafts反应得到了目标产物的类似物1-甲基-2-甲氧羰基-3-羟基-6，7，8-三甲氧基蒽醌（路线1）。目标产物及其它类似物的合成正在进行中。 2．以乙酰乙酸甲酯和巴豆醛为原料，经过Michael加成、分子内的Aldol反应、芳香化、选择性甲酰化和还原反应，得到关键中间体2-甲基-3-羟甲基-6-甲氧基苯甲酸甲酯及其衍生物。通过该化合物与3，4，5-三甲氧基苯甲酸甲酯进行Friedel-Crafts烷基化反应得到了多取代的二苯基甲烷衍生物，拟进一步关环合成目标化合物（路线2）。 3．发现邻甲氧基苯甲酸甲酯中酯甲基可以被正丁基锂和仲丁基锂中烷基交换生成相应的酯，反应的机理不明确。当使用叔丁基锂时，得到的是邻甲氧基苯基叔丁酮，这个方法可以用来合成芳基叔丁酮类化合物。 4．以2-苄氧基-6-甲基苯甲酸甲酯为原料进行氯甲基化反应时，以苯和二氯乙烷作溶剂，发生了苄基的迁移和芳环的偶联，分别得到2，2'-二甲基-3，3'-二甲氧羰基-4，4'-二羟基联苯和2，2'-二甲基-3，3'-二甲氧羰基-4，4'-二羟基-5，5'-二苄基联苯。这是对称联苯合成的新方法。 5．水杨酸羟基邻对位的选择性甲酰化可以分别通过水杨酸和水杨酸甲酯用HMTA/CF3COOH来实现。 6．Lewis酸催化3，4，5-三甲氧基苄醇环化成1, 2, 3, 6, 7, 8, 11, 12, 13-nonamethoxyl-10,15-dihydro-5H-trbibenzo [a, d, g] cyclononene (NDTC)，产率(54%)高于已有方法（12%）。 Methyl 3,6,8-trihydroxy-7-methoxy-1-methylanthraquinone-2-carboxylate is a new COX-2 selective inhibitor isolated from Gladiolus gandavensis. Two strategies were investigated to synthesis this compound, in which some important reactions were discovered. 1. The key intermediate 5-hydroxy-3-methylbenzene-1,2,4-tricarboxylic acid 2,4-dimethyl ester was prepared via Diels-Alder reaction followed by selective hydrolysis of 1-COOMe. This compound was coupled with 1,2,3-trimethoxybenzene and the product undergo intramolecular Friedel-Crafts reaction to give methyl 3-hydroxy-5,6,7-trimethoxy-1-methylanthraquinone-2-carboxylate (1st route). The target compound and other analogues are being prepared with the same procedure. 2. The key intermediates methyl 3-hydroxymethyl-6-methoxy-2-methylbenzoate and its derivatives were prepared starting from crotonaldehyde and methyl acetoacetate via Michael addition, intramolecular aldol reaction, aromatization, formylation and reduction. The intermediates were coupled respectively with derivatives of gallic acid to give polysubstituted diphenylmethane. However, attempts to cyclize these compounds to the target compounds and analogues were not successful (2nd route). 3. In the process for ortho-lithiation of methyl 2-methoxybenzoate, the substrate converted respectively to n-butyl 2-methoxybenzoate and sec-butyl 2-methoxybenzoate when n-BuLi and sec-BuLi were used. However, tert-BuLi reacted with methyl 2-methoxybenzoate afford 2-methoxyphenyl tert-butyl ketone, which could be used to synthesize aryl tert-butyl ketones. 4. The transformtion of methyl 2-benzoxy-6-methylbenzoate to dimethyl 4,4'-dihydroxy-2,2'-dimethylbiphenyl-3,3'-dicarboxylate in benzene, and dimethyl 5,5'-dibenzyl-4,4'-dihydroxy-2,2'-dimethylbiphenyl-3,3'-dicarboxylate in 1,2-dichloroethane in the presence of ZnCl2 provides a new method for the synthesis of symmetric biphenyl. 5. The formylation of salicylic acid at C-5 and methyl 2-hydroxybenzoate at C-3 could be regioselectively realized by using HMTA/CF3COOH. 6. Racemic 1, 2, 3, 6, 7, 8, 11, 12, 13-nonamethoxyl-10, 15-dihydro-5H-trbibenzo [a, d, g] cyclononene was prepared via Lewis acids catalyzed trimerization of 3, 4, 5-trimethoxylbenzyl alcohol with yield (54%) higher than the reported procesure (12%).

N-烷基氮杂糖及其衍生物的合成

多羟基哌啶类化合物通常称为氮杂糖，由于与糖结构的相似性，亚胺基环醇表现出强的糖苷酶和糖基转移酶抑制活性，可调控在生物识别及酶结构控制中起到重要作用的糖蛋白的生物合成与水解。因此这类抑制剂有望成为与糖代谢紊乱有关的疾病的治疗药物，如：抗糖尿病、抗肿瘤、抗溶酶体贮积症及抗病毒感染（包括艾滋病）等药物。正是由于氮杂糖的重要生物活性及诱人的药用开发前景，近年来，有关氮杂糖及其衍生物的合成、生物活性及应用研究备受关注。 本论文探索了一系列的作为潜在的迈克加成中间体1-C-乙酰甲基/甲氧羰基甲基-5-N-取代呋喃核糖碳苷衍生物在碱的作用下先发生β-消除反应，接着发生分子内的迈克加成反应生成1-C-乙酰甲基-N-取代氮杂吡喃糖碳苷衍生物及1-C-甲氧羰基甲基-N-取代氮杂吡喃糖碳苷衍生物的方法，该转变过程为先通过β-消除得到非环状的α/β不饱和共轭酮或酯的中间体，接着5-N-取代氨基与分子内的α/β不饱和共轭酮或酯发生分子内的1,4-亲核加成，其中，2'-酯的环加成立体选择性的得到β型1-C-乙酰甲基-N-取代氮杂吡喃糖碳苷衍生物，而2'-酮的环加成得到立体异构体1-C-乙酰甲基-N-取代氮杂吡喃糖碳苷衍生物。此外，该类N-取代氮杂吡喃糖碳苷衍生物进一步脱除保护基，得到了一系列新的N-取代氮杂吡喃糖衍生物，拓展了氮杂吡喃糖碳苷分子库。 中间体1-C-(2'-oxoalkyl)-5-N-alkylated glycoribofuranoside的合成是由核糖为原料，通过对其结构修饰，在C-5氮原子上先引入不同的取代基，在C-1上引入乙酰甲基或甲氧羰基甲基。C-5取代氨基的引入通过两种方法：(a) 5-取代链状脂肪氨基可由链状的伯胺直接与5-甲磺酰基发生SN2亲核取代得到；(b) 5-取代芳香氨基可通过芳香醛与C-5氨基缩合再由硼氢化钠还原得到。2'-酰基的引入通过烯丙基氧化得到：2'-酮羰基由醋酸汞和琼斯试剂氧化得到；2'-酯基由高锰酸钾氧化再碘甲烷的作用下得到。 The polyhydroxylated piperidines, commonly be called azasugars. Iminocyclitols and their derivatives have exhibited remarkable biological activity to inhibit glycosidase-processing enzymes, with resulting potential chemotherapeutic applications against diabetes, cancer, lysosomal storage disorders and viral infections including AIDS. Recently, because of the important biological activity and excellent foreground on pharmaceutical application, great attention has been attracted to the synthesis of the new derivatives and analogues. In this dissertation, 1-C-(2'-oxoalkyl)-5-N-substituted-glycoribofuranosides, which used as latent substrates for intramolecular hetero-Michael addition, were converted to 2-ester and 2-ketone aza-C-glycopyranosides by base treatment. The transformation was achieved through β-elimination to an acyclic α/β-conjugated ketone or ester, followed by an intramolecular hetero-Michael addition by the 5-N-alkylated amino group. The 2-ester cycloaddition was highly stereoselective in favor of an equatorial 1-C-substitution while the 2-ketone cycloaddition was produced a pair of stereoisomers of 2′-ketonyl aza-C-glycoside. Additionally, the resultant different N-alkylated aza-C-glycopyranosides could be further prepared for various azasugar library constructions by removal of protecting groups. Synthesis of the key intermediate 1-C-(2'-oxoalkyl)-5-N-alkylated glycoribo- furanoside involved the introduction of 5-substituted amino and 1-C-2′-oxoalkyl groups from D-ribose. The 5-alkylated amino was introduced through two methods: (a) the 5-aliphatic series amino synthesized by the nucleophilic substitution of 5-mesylate using neat ethylamine, propylamine, butylamine, and hexylamine, (b) the 5-aromatic series amino synthesized by various aromatic aldehydes with C-5 amino under NaBH4 reduction. The 1-C-2′-oxoalkyl groups were introduced through oxidation of the ally group: the 1-C-allyl group was oxidized with Hg(OAc)2 and Jones reagent to the 2-ketonyl C-glycoside; the 1-C-allyl group was oxidized with KMnO4 and CH3I/NaHCO3 to 1-C-methyl acetate glycoside.

A Facile One-pot Synthesis of Substituted Pyridine-2,4(1H,3H)-diones from α-Acyl-α-carbamoyl Ketene-S,S-acetals

A facile and efficient one-pot synthesis of substituted pyridine-2,4(1H,3H)-diones has been developed. Subjected to N,N-dimethylformamide dimethyl acetal (DMFDMA) in N,N-dimethylformamide at 120 ˚C, a series of acyl(carbamoyl)ketene S,S-acetals were converted into the corresponding substituted pyridine-2,4(1H,3H)-diones in high yields.

Synthesis of novel star-like hyperbranched polymers with poly(amido amine) core and poly(L-lysine) shell

Hyperbranched poly(amido amine)s containing vinyl and hydroxyl groups were successfully synthesized via Michael addition polymerization of triacrylamide (TT) and 3-amino-1,2-propanediol (APD) with equal molar ratio in feed. H-1, C-13 and HSQC NMR techniques were used to clarify the structure of hyperbranched polymers and polymerization mechanism.

Synthesis and micellization of star-like hyperbranched polymer with poly(ethylene oxide) and Poly(epsilon-caprolactone) arms

Novel star-like hyperbranched polymers with amphiphilic arms were synthesized via three steps. Hyperbranched poly(amido amine)s containing secondary amine and hydroxyl groups were successfully synthesized via Michael addition polymerization of triacrylamide (TT) and 3-amino-1,2-propanediol (APD) with feed molar ratio of 1:2. H-1, C-13, and HSQC NMR techniques were used to clarify polymerization mechanism and the structures of the resultant hyperbranched polymers

One-pot synthesis and characterization of hyperbranched poly(ester-amide)s from commercially available dicarboxylic acids and multihydroxyl secondary Amines

A convenient and cost-effective strategy for synthesis of hyperbranched poly(ester-amide)s from commercially available dicarboxylic acids (A(2)) and multihydroxyl secondary amine (CB2) has been developed. By optimizing the conditions of model reactions, the AB(2)-type intermediates were formed dominantly during the initial reaction stage. Without any purification, the AB(2) intermediate was subjected to thermal polycondensation in the absence of any catalyst to prepare the aliphatic and semiaromatic hyperbranched poly(ester-amide)s bearing multi-hydroxyl end-groups.

SYNTHESIS AND CHARACTERIZATION OF A CROSSLINKING POLYETHYLENIMINE AS SMART GENE CARRIER AND EFFECTS OF PEGYLATION DEGREE

A smart biodegradable cationic polymer (CBA-PEI) based on the disulfide bond-containing cross-linker cystamine bisacrylamide (CBA) and low molecular weight branched polyethylenimine (1800-Da, PEI1800) was successfully synthesized by Michael addition reaction in our recent study. Furthermore, a series of copolymers (CBA-PEI-PEG) with different PEGylation degree were obtained by the mPEG-SPA (5000-Da) reacting with CBA-PEI at various weight ratios directly. The molecular structures of the resulting polymers CBA-PEI and CBA-PEI-PEG were evaluated by nuclear magnetic resonance spectroscopy (H-1-NMR) and capillary viscosity measurements, all of which had successfully verified formation of the copolymers. The polymer/DNA complexes based on CBA-PEI and CBA-PEI-PEG were measured by dynamic light scattering and gel retardation assay. The results showed that the particle size and zeta potential of complexes were reduced with increasing amount of PEG grafting, even no particle formation. The particle size of CBA-PEI/DNA complexes was in range of 103.1 to 129.1 nm, and the zeta potential was in range of 14.2 to 24.3 mV above the 2:1 weight ratio. In the same measure condition, the particle size of CBA-PEI-PEG complexes was reduced to a range of 32.2 to 55 nm, and the zeta potential was in range of 9.3 to 13.8 mV at the 2:1 weight ratio.

Synthesis and structural characterization of (pyrazolyl)alkenyl Fischer carbene complexes of chromium and tungsten

Michael addition of substituted pyrazoles 2 to 1-alkynyl Fischer carbene complexes (CO)(5)M=C(OEt)(CdropCPh) (1) (a, M = Cr and b M = W) afforded (pyrazolyl)alkenyl Fischer carbene complexes (CO)(5)M=C(OEt)(CH=C(R(1)R(2)R(3)pz)Ph) (R(1)R(2)R(3)pz = pyrazolyl) 3 (M = Cr) and 4 (M = W), respectively, with an exclusive (E)-configuration in mild to excellent yields. The reaction of la and 3,5-dimethylpyrazole (2b) was monitored to demonstrate the formation and decomposition of complex 3b by H-1 NMR measurements in CDCl3 at 23degreesC. Complexes 3 and 4 were characterized with H-1, C-13{H-1} NMR, IR spectroscopies and elemental analysis. When the substituted pyrazoles were 3-methylpyrazole (2a) and 3,5-di-tert-butylpyrazole (2d), molecular structures of the corresponding (pyrazolyl)alkenyl Fischer carbene complexes 3a and 4d were characterized by X-ray crystallographic study. (C) 2004 Elsevier Ltd. All rights reserved.

A Concise Approach to a Gelsemine Core Structure using an Oxygen to Carbon Bridge Swapping Strategy

A tricyclic core structure related to gelsemine was synthesized from an oxabicyclo[3.2.1]octanone by a three-step bridge swapping strategy involving elimination of the bridging ether oxygen and intramolecular Michael addition of a tethered cyanoacetamide unit.

S-(2-Succinyl)cysteine:a novel chemical modification of tissue proteins by a Krebs cycle intermediate

S-(2-Succinyl)cysteine (2SC) has been identified as a chemical modification in plasma proteins, in the non-mercaptalbumin fraction of human plasma albumin, in human skin collagen, and in rat skeletal muscle proteins and urine. 2SC increases in human skin collagen with age and is increased in muscle protein of diabetic vs. control rats. The concentration of 2SC in skin collagen and muscle protein correlated strongly with that of the advanced glycation/lipoxidation end-product (AGE/ALE), N(epsilon)-(carboxymethyl)lysine (CML). 2SC is formed by a Michael addition reaction of cysteine sulfhydryl groups with fumarate at physiological pH. Fumarate, but not succinate, inactivates the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase in vitro, in concert with formation of 2SC. 2SC is the first example of spontaneous chemical modification of protein by a metabolic intermediate in the Krebs cycle. These observations identify fumarate as an endogenous electrophile and suggest a role for fumarate in regulation of metabolism.