白藜芦醇类似物的合成

3,5-二甲氧基苄溴(4)与NaCN反应生成3,5-二甲氧基苄腈(5), 5经水解得到3,5-二甲氧基苯乙酸(6). 5与苯甲醛或取代苯甲醛发生Knoevenagel反应生成化合物2a～2d, 为Z式构型. 6与苯甲醛或取代苯甲醛发生Perkin反应得到化合物3a～3c, 为E式构型. 2a～2d和3a～3c均为白藜芦醇类似物. 给出了各步反应产物的IR, ¹H NMR, ¹³C NMR和MS数据, 讨论了影响反应的因素, 并给出了化合物2a～2d和3a～3c对乳腺癌细胞MCF-7、肺癌细胞H446、乳腺癌细胞231的体外生理活性和对正常肝细胞L02体外毒性的半致死浓度.     

奈必洛尔的不对称合成

首先合成4-氟-2-(5-羟基戊烷基-3-烯)-苯酚(2), 再经Sharpless不对称环氧化等反应分别得到2-氨基-1-[6-氟- (2S)-3,4-二氢-2H-2-苯并吡喃]-(1R)-1-乙醇(6)和6-氟-2-[(2R)-2-环氧乙烷基]-(2R)-3,4-二氢苯并吡喃(10). 最后, 6和10发生亲核开环反应即得到目标产物奈比洛尔. 整个合成路线简单易行, 并在原有文献的基础上有较大改进, 使收率大大提高, 总收率由文献的2.1%提高到14.1%.     

Synthesis of Novel Cyclodextrin Trimers

CD trimers (3 and 6) and CD dimers (4 and 7) have been synthesized by reaction of 6-deoxy-6-hydroxyethylamino-β-CD (1) with corresponding 1,3,5-tri(bromomethyl) benzene (2) or 1,3,5-tri (bromomethyl)-2,4,6-trimethylbenzene (5) in the presence of base.     

A Total Synthesis of Isosolanone

Nitroaldol reaction of acetone with nitromethane in the presence of base to give a nitroalcohol 3, followed by acetylation, and subsequent reduction of the resultant acetate 4 with NaBH₄ gave 2-methyl-1-nitropropane 5. Michael reaction of 5 in base with acrylonitrile to give nitronitrile 6, and Nef conversion of the nitro group resulted in the corresponding ketonic nitrile 7. Wittig olefination of the ketonic nitrile with 3-methyl-2-butenyl triphenylphosphonium bromide 8 gave dienenitrile 9, which upon treatment with MeLi, followed by acidic work up, provided isosolanone 2.     

Synthesis of Streptazoline Glucopyranosides

Abstract

The antibacterial properties of streptazoline (1),² isolated as a lipophilic neutral component from Streptomyces viridochromogenes,³ were recognized to be attributed to the formation of chartreusine.⁴ The pure compound 1 is rather labile due to the presence of the diene part, which enhances its polymerization. However, it may be kept for some time, in diluted solutions at low temperatures. Recently, the total synthesis of streptazoline (1) was reported,⁵ based on an azaanalogue Ferrier rearrangement.⁶ The catalytic hydrogenation of the compound 1 afforded the stable dihydrostreptazoline (4) which possessed lower antibacterial and antifungal activities than streptazoline (1) itself.⁷ X-ray studies of 5-acetoxydihydrostreptazoline (5) showed that it contained an internal urethane structure.     

Synthesis of Homogalacturonan Fragments

ABSTRACT

Glycosylation of the D-galacturonic acid ester derivatives 15 and 17, which are prepared directly from D-galacturonic acid, with the thioglycosides 28 and 32, derived from the same sugar, provides α(1→4)-linked dimers. The formation of the glycosidic linkage between the galacturonic acid moieties is best achieved by iodonium di-sym-collidine perchlorate promotion. Thus, the 4'-O-p-methoxybenzyl dimer 38 can be obtained in 64% yield. Partial deprotection of the 4'-O-position provided the glycosyl acceptor 36, which was coupled with the donor 32 to yield the α(1”→4')-linked trimer 39 (48%). Approximately 8% of the β(1”→4')-coupled isomer was observed in the ¹³C NMR spectrum of the reaction mixture.     

One Pot Synthesis of Aryldiazepinothiophenones

Abstract

Aryldiazepinothiophenones 2 were prepared from the reaction of o-phenylenediamines with acetone in the presence of 2-mercaptopropionic acid. Fused thiazolobenzodiazepines 3 along with fused thiazolobenzimidazoles 4 and 1,5-benzodiazepines 5 were obtained as by-products. The benzodiazepinothiophenone 2a and the benzodiazepine 5a were also isolated from the reaction of o-phenylenediamine with phorone.     

Synthesis of Pyridothienopyridines and Arylazothienopyridines

Treatment of aminothienopyridine 3 with arylidenemalononitrile afford pyridothienopyridine 4. Also condensation of 3 with ethyl ethoxymethylene-cyanoacetae afford compound 5, which was cyclized in diphenyl ether into pyridothienopyridine 6. Thiourea derivative 7 was cyclized using Br₂/AcOH, and ethyl chloroacetate to afford thiazolothienopyridine 8 and thiazolidinylthienopyridine 9 respectively. Compound 15 was condensed with aromatic aldehydes to give the corresponding arylidenethienopyridines 16a–d. The latter compounds were underwent Michael addition with malononitrile to produce pyranothienopyridines 17a–d. Compound 15 was coupled with aromatic diazonium chloride to give the corresponding 2-arylazothienopyridine derivatives 20, but when treated with nitrous acis it dimerised into compound 19.     

Synthetic Utility of Enaminonitrile Moiety in Heterocyclic Synthesis: Synthesis of Some New Thienopyrimidines

The hitherto unknown 3-amino-5-bromo-4, 6-dimethylthieno [2, 3-b] pyridine-2-carbonitrile ( 4 ) was condensed with p-anisaldehyde affording the Schiff base ( 5 ). Acylation of the thienopyridine derivative ( 4 ) using freshly distilled acetic anhydride gave a mixture of mono and diacetyl derivatives ( 6 ) and ( 7 ). Condensation of ( 4 ) with triethylorthoformate yielded the ethoxymethyleneamino derivative ( 8 ), which was treated with hydrazine hydrate to give the hydrazide derivative ( 9 ), which in turn was converted to a triazolopyrimidine derivative ( 10 ) upon treatment with freshly distilled acetic anhydride. Thiation of ( 4 ) with carbon disulfide afforded the pyrimidine dithione derivative ( 11 ), which was alkylated with ethyl iodide to give the di-s-ethylpyrimidine derivative ( 12 ).On the other hand, treatment of ( 4 ) with formamide yielded the aminopyrimidine derivative ( 13 ), whereas its treatment by formic acid produced the thienopyrimidinone derivative (1 4 ). Chlorination of (1 4 ) with a mixture of phosphorus pentachloride and phosphorus oxychloride gave the chloropyrimidine derivative ( 15 ), which in turn afforded the hydrazide derivative ( 9 ) upon treatment with hydrazine hydrate. Hydrazinolysis of ethyl-3-amino-5-bromo-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate ( 17 ) gave the hydrazino derivative ( 18 ), which in turn was converted to 8-bromo-7,9-dimethyl-3-formylaminopyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one ( 19 ) and 8-bromo-3-diacetylamino-2,7,9-trimethylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one ( 20 ) upon treatment with formic acid and freshly distilled acetic anhydride, respectively.     

Nitrones in Organic Synthesis. Synthesis of Secondary Allyl Amines

Nitrones 1 undergo addition of vinyl organomagnesium bromide to give the allyl hydroxylamines 3 which are easily reduced to the corresponding N-benzyl allyl amines 2.     

Synthesis of Valganciclovir Hydrochloride Congeners

Valganciclovir hydrochloride (1) is used for the treatment of cytomegalovirus (CMV) retinitis in patients with weakened immune systems. Valganciclovir hydrochloride is a hydrochloride salt of L-valyl ester of ganciclovir (2) that exists as a mixture of two diastereomers. According to the U.S. Food and Drug Administration specifications, the diastereomeric ratio of valganciclovir hydrochloride 1 should be maintained in the range 55:45 to 45:55. According to the U.S. Food and Drug Administration specifications, the diastereomeric ratio of valganciclovir hydrochloride 1 should be maintained in the range 55:45 to 45:55. During the process development of valganciclovir hydrochloride, six related substances (impurities) were observed along with the final active pharmaceutical ingredient. Among these six impurities, ganciclovir (2) and guanine (3) are the key starting materials and degraded impurities of ganciclovir, respectively. The remaining four impurities were identified as isovalganciclovir hydrochloride (4), methoxymethylguanine (5), O-acetoxy ganciclovir (6), and isovalarylganciclovir (7). The present work describes the synthesis and characterization of these four impurities.     

Synthesis of Some Bicyclic Thiazolopyrimidine Derivatives

Thiazolopyrimidine compounds 3(a–d) were synthesized by a simple one-pot condensation reaction of starting pyrimidine derivative 1 and 1,2-dibromoethane 2 in dimethylformamide. In a similar way thiazolopyrimidine compounds 5(a–e) were synthesized by reaction of 1 and 2-bromopropionic acid 4 in dioxane under reflux condition. The yields of products following recrystallization from ethanol were of the order of 70–80%.     

Synthesis of Repaglinide Congeners

This report describes a synthesis of two potent impurities of repaglinide, benzyl repaglinide 1 and repaglinide isomer 2, from commercially available raw materials: 2-fluoro benzonitrile, (S)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butylamine (5), and 3-ethoxy-[4-(ethoxycarbonyl)phenyl]acetic acid (7). These impurities are the crucial components in determining the quality of the drug substance, repaglinide, during its manufacturing.     

Short Synthesis of Pulchellalactam

tert‐Butyl 4‐methyl‐2‐oxo‐2,5‐dihydro‐1H‐pyrrole‐1‐carboxylate 4 was synthesized by a short two‐step procedure: regioselective 1,3‐dipolar diazomethane cycloaddition to N‐Boc‐pyrrolinone 2 and thermolysis of the adduct. The compound 4 could be converted in one step into pulchellalactam.     

Short Synthesis of Functionalized Cyclic Homoallylsilanes

The synthesis of functionalized cyclic homoallylsilanes 5 and 6 was described starting from functional cycloalkenols 1 and 2, in which the addition of silylcuprate to the functional acetates 3 and 4 were used as the key reaction step.     

Synthesis of Trichlorophenol Derivatives

An expedient three‐step procedure for the synthesis of trichlorophenol derivatives based on the acid‐catalyzed rearrangement of the bicyclic ketone precursors 6a–e in high overall yield is described. The bicyclic ketone precursors 6a–e were obtained from Diels–Alder cycloadducts of β‐substituted vinyl acetates with tetrachloro‐5,5‐dimethoxycyclopentadiene in two steps.     

Synthesis of Deoxytabtoxinine-β-Lactam

Deoxytabtoxinine-β-lactam (12) was synthesized in 6 steps from 3. β-Lactam 12 does not inhibit glutamine synthetase indicating that the hydroxyl group of tabtoxinine-β-lactam (2) is necessary for inhibition of glutamine synthetase.     

Synthesis of diterpene glycosides

Summary Mono-, di-, and linear triglycosides of a diterpene alcohol, derived from abietic acid and glucose have been synthesized employing peracetylbromo--D-glucose (4) and maltose derivatives5 and8 as glycosyl donors. The triglycoside14 exhibits slight haemolytic activity.

---

Synthese von Diterpenglycosiden

Zusammenfassung Es wird die Synthese von Mono-, Di-, und linearen Triglycosiden aus einem von Abietinsäure abgeleiteten Diterpenalkohol beschrieben. Als Glycosyldonoren wurden neben Peracetobrom--D-glucose (4) die Maltosederivate5 und8 verwendet. Das Triglycosid14 zeigt schwache hämolytische Aktivität.

     

Practical Synthesis of Sinigrin

Abstract

Sinigrin (1), the most commonly known glucosinolate, is a naturally occurring thiosugar, widely distributed in the botanic family Cruciferae. Sinigrin was first isolated in 1839 from seeds of black mustard in the form of its potassium salt.¹ Commercially available sinigrin is obtained by extraction from horseradish.² So far a number of natural glucosinolates and their analogs have been synthesized.^3-10 The only synthesis of compound 1, leading to a crystalline product on the miligram scale, has been reported by Benn and Ettlinger³ (Scheme 1). Their procedure has been applied by Kjaer and Jensen⁴ for the synthesis of the higher homologue of sinigrin (1), but no information of the overall yield has been provided.     

Regiospecific Synthesis of Bikaverin

A regiospecific synthesis of bikaverin (1) is described starting from methyl 2-hydroxy-4-methoxy-6-methyl benzoate (2) and 2-chloro-5,7-dimethoxy-1,4-naphoquinone (4).