The Asymmetric Syntheses of Methyl <small>D</small>-Digitoxoside, <small>L</small>-Oleandrose and <small>L</small>-Cymarose from Methyl Sorbate, an Achiral Precursor

The addition of 4?eq of chloral to osmundalactone (4S,5R)-4 gave quantitative formation of the hemiacetal derivative (4S,5R)-8, which was treated with methane sulfonic acid to afford the intramolecular Micheal addition product (+)-(3S,4S,5R)-9 possessing a 3,4-cis-dihydroxy-δ-lactone in 78% overall yield from (4S,5R)-4. The obtained (+)-(3S,4S,5R)-9 was subsequently converted to methyl D-digitoxoside (pyranoside) (12) in 13% overall yield and methyl D-digitoxoside (furanoside) (12) in 20% overall yield. The reaction of benzyl-osmundalactone (4R,5S)-3 and MeOH in the presence of Amberlyst A-26 as a basic catalyst gave 3,4-trans-δ-lactone (－)-(3S,4R,5S)-20 in 28% yield and 3,4-cis-δ-lactone (－)-(3R,4R,5S)-21 in 45% yield. Dibal-H reduction of (－)-(3S,4R,5S)-20 followed by catalytic hydrogenation gave L-oleandrose (6) in 86% overall yield, while Dibal-H reduction of (－)-(3R,4R,5S)-21 followed by catalytic hydrogenation provided L-cymarose (7) in 85% overall yield.     

加兰他敏重要中间体溴那维定的合成

以6-溴异香草醛和酪胺为原料,经一锅法进行连续的两步还原胺化制得N-甲基-N-(4-羟基苯乙基)-2-溴-5-羟基-4-甲氧基苯甲胺(4),收率85%。以5%聚乙二醇为相转移催化剂,氯仿为溶剂,铁氰化钾为氧化剂,对4进行氧化偶联,合成了加兰他敏的重要中间体溴那维定,收率39%,其结构经1H NMR,IR和MS确证。     

2,2-二甲基-3,4-二溴-7,8-二乙酸基色烯的合成

本文合成了2,2-二甲基-3,4-二7,8-二乙酸基色烯,主要想通过溴的引入改变色烯3,4位双键的性质,视其对活性的影响, 也为用溴标记探讨这类激素在昆虫体内参与细胞蛋白烷基化的代谢过程提供一条途径。色满/D 5     

氯雷他定的合成

以N-甲基-4-哌啶酮和8-氯-10,11-二氢-4-氮杂-5H-二苯并[a,d]-5-环庚酮为原料,经McMurry反应得到8-氯-6,11-二氢-11-(1-甲基-4-哌啶烯基)-5H-苯并[5,6]庚环[1,2-b]吡啶,收率为83.9%,最后与氯甲酸乙酯反应得到氯雷他定,总收率为35.7%。对McMurry反应过程中产生的副产物3、4进行了分离、表征。     

Total synthesis of (-)-indolactam V

The total synthesis of protein kinase C activator (-)-indolactam V (IL-V) has been successfully completed with two separate approaches: From known 4-nitrotryptophan derivative 3 in 8 steps (49% overall yield) and from L-glutamic acid in 12 steps (18% overall yield), where 4-nitrotryptophanol derivative 4 served as a key intermediate. Derivatives 3 and 4, both incorporating indole 4-substitution and the C-9 stereocenter in IL-V, were synthesized via the Pd-catalyzed indole synthesis from 3-nitro-2-iodoaniline 5 with aldehydes 6 and 7, respectively. Aldehyde 7 was, meanwhile, synthesized from l-glutamic acid in 5 steps (68% yield). Lactamization of the 9-membered ring was achieved using HATU in THF in good yield.     

褪黑激素的合成与表征

以吲哚为起始原料,经4步反应合成了褪黑激素(MLT) 吲哚(1)在甲醇中羟基化得到5-羟基吲哚(2),(2)同2-氯乙胺在乙酸乙酯中进行胺乙基化反应得到5-羟基色胺(3),(3)与硫酸二甲酯在甲苯中对羟基进行醚化,得到5-甲氧基色胺(4),(4)经乙酰化得到产物MLT,收率80%     

Selenium dioxide oxidations of dialkyl-3H-azepines: the first synthesis of 2-azatropone from oxidation of 2, 5-Di-tert-butyl-3H-azepine

Oxidation reactions of 2,5- and 3,6-di-tert-butyl-3H-azepines (1 and 2) with selenium dioxide (SeO(2)) were performed. The oxidation of 1 with SeO(2) gave 3-tert-butyl-7,7-dimethyl-4-oxo-octa-2,5-dienal 3 in 36% yield, 4-tert-butyl-5-(3,3-dimethyl-2-oxo-butylidene)-1, 5-dihydro-pyrrol-2-one 4 in 13% yield, 2, 6-di-tert-butyl-2-pyridinecarbaldehyde 5 in 12% yield, and 4, 7-di-tert-butyl-2H-azepin-2-one (2-azatropone) 6 in 6% yield, respectively. Oxidation of 2 with SeO(2) gave 2, 2-dimethyl-1-[2-(5-tert-butyl)-pyridyl]propanol 7 in 55% yield, and 3,6-di-tert-butyl-2H-azepine 8 in 5% yield, respectively. We found that selenium dioxide oxidation of 1 affords 4-oxo-octa-2,5-dienal 3 by a new ring cleavage reaction of 1, and we described the first synthesis of 2-azatropone 6 from this oxidation of 1. In the case of 2, pyridylpropanol 7 was obtained as the major product. We now report in detail result of these oxidation reactions, which have led to the synthesis of a novel azatropone derivative.     

Electrosynthesis of 5-amino-4-oxopentanoic acid hydrochloride

The electroreduction of methyl 5-nitro-4-oxopentanate was studied by means of a polarographic method and preparative electrolysis in acidic-alcoholic solutions. The effects of the following factors on the yield and quality of 5-amino-4-oxopentanoic acid hydrochloride were studied: the cathode material, amount of electricity, temperature, nature of the solvent, concentrations of the initial nitro compound and hydrochloric acid, and the cell design. It was shown by electrolysis at a controlled potential and in a galvanostatic mode that the products of methyl 5-nitro-4-oxopentanate electroreduction are hydroxyamino and amino compounds, and also ammonium chloride, nitromethane, methylhydroxylamine hydrochloride, and monomethylamine hydrochloride. Their ratio depends on the electrolysis conditions. The highest overall substance yield (61.1–66.0%) and current yield (68.1–68.6%) of 5-amino-4-oxopentanoic acid hydrochloride was achieved at a copper cathode in a filter-press cell. The content of the main substance in the electrochemically obtained samples of 5-amino-4-oxopentanoic acid was 89.5–91.0%.     

Heterogeneous-catalytic fischer reaction. 13. Catalytic synthesis of 4-, 5-, 6-, and 7-methoxyindoles

Methoxy-substituted acetaldehyde phenylhydrazones were cyclized in the vapor phase on a GIPKh-115 catalyst to give 4-, 5-, 6-, and 7-methoxyindoles. 5-Methoxyindole was obtained in 50% yield, 4- and 6-methoxyindoles were obtained in 85% yield, and 7-methoxyindole was obtained in 45% yield.See [1] for Communication 12.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1054–1055, August, 1982.     

脂蛋白脂酶激活剂艾溴利平类似物的合成

合成了两个新型的艾溴利平类似物——N-2 -硝基-4-氯苯基-4-[(膦酸二乙酯基)甲基]苯甲酰肼(5,总收率28.1％)和N-2-四氮唑基-4-氯苯基-4-[(膦酸二乙酯基)甲基]苯甲酰胺(7,总收率30.5％).以对氯甲基苯甲酸为原料,经酯化、水解和酰氯反应制得中间体4-[(膦酸二乙酯基)甲基]苯甲酰氯(4);4与2-硝基-4-氯苯肼盐酸盐反应合成了5.4先与2-氨基-5-氯苯腈反应制得N-2-氰基-4-氯苯基-4-[(膦酸二乙酯基)甲基]苯甲酰胺(6);6再与叠氮化钠反应合成了7.其结构经1 H NMR和IR表征.     

Studies on enaminonitriles: A new synthesis of 1,3‐substituted pyrazole‐4‐carbonitrile

3‐Diethylaminoacrylonitrile ( 1 ) reacts with hydrazonyl halides ( 2a‐d ) to yield 1,3‐disubstituted pyrazole‐4‐carbonitriles 5a‐d. The acetyl 1‐p‐chlorophenylpyrazole‐4‐carbonitrile ( 5a ) condensed with hydrazine hydrate to yield the bishydrazone 10 and with dimethylformamide dimethylacetal to yield 1‐aryl‐3‐(3‐dimethylamino)acryloyl pyrazole‐4‐carbonitrile ( 11 ). This enamine reacts with hydrazine hydrate to yield the pyrazolylpyrazole ( 12 ) and with naphthoquinone to yield the 3‐naphthofuranoyl pyrazole 13. The pyra‐zolyl pyridine derivative 14 was obtained upon treatment of 11 with acetylacetone in the presence of ammonium acetate. Compound 11 was coupled with p‐chlorobenzene diazonium chloride to yield the hydrazone 16 that was coupled further with p‐chlorobenzenediazonium chloride to yield the formazane 18.     

Reductive degradation of nido-1-CB8H12 into smaller-cage carborane systems via new monocarbaboranes [arachno-5-CB8H13](-) and closo-2-CB6H8

Treatment of the nido-1-CB8H12 (1) carborane with NaBH4 in THF at ambient temperature led to the isolation of the stable [arachno-5-CB8H13]- (2(-)), which was isolated as Na+[5-CB8H13]-.1.5 THF and PPh4 +[5-CB8H13]- in almost quantitative yield. Compound 2(-) underwent a boron-degradation reaction with concentrated hydrochloric acid to afford the arachno-4-CB7H13 (3) carborane in 70 % yield, whereas reaction between 2(-) and excess phenyl acetylene in refluxing THF gave the [closo-2-CB6H7]- (4-) in 66 % yield. Protonation of the Cs+4(-) salt with concentrated H2SO4 or CF3COOH in CH2Cl2 afforded a new, highly volatile 2-CB6H8 (4) carborane in 95 % yield, the deprotonation of which with Et3N in CH2Cl2 leads quantitatively to Et3NH+[2-CB6H7](-) (Et3NH+4(-)). Both compounds 4- and 4 can be deboronated through treatment with concentrated hydrochloric acid in CH2Cl2 to yield the carbahexaborane nido-2-CB5H9 (5) in 60 % yield. New compounds 2-, 3, and 4 were structurally characterised by the ab initio/GIAO/MP2/NMR method. The method gave superior results to those carried out using GIAO-HF when relating the calculated 11B NMR chemical shifts to experimental data.     

IR kinetic spectroscopy investigation of the CH4 + O(1D) reaction

The branching of the title reaction into several product channels has been investigated quantitatively by laser infrared kinetic spectroscopy for CH(4) and CD(4). It is found that OH (OD) is produced in 67 +/- 5% (60 +/- 5%) yield compared to the initial O((1)D) concentration. H (D) product is produced in 30 +/- 10%(35 +/- 10%). H(2)CO is produced in 5% yield in the CH(4) system (it was not possible to measure the CD(2)O yield in the CD(4) case). D(2)O is produced in 8% yield in the CD(4) system (it was not feasible to measure the H(2)O yield). The ratio of the overall rate constant of the CD(4) reaction to the overall rate constant of the O((1)D) + N(2)O reaction was determined to be 1.2(5) +/- 0.1. A measurement of the reaction of O((1)D) with NO(2) gave 1.3 x 10(-10) cm(3) molecule(-1) s(-1) relative to the literature values for the rate constants of O((1)D) with H(2) and CH(4). Hot atom effects in O((1)D) reactions were observed.     

三种O－异戊烯基苯丙素类天然产物的首次合成

以香草醛为起始原料，经O－异戊烯基化、Witting反应、水解、还原、氧化等 反应步骤，首次合成了三种苯丙素天然产物boropinalA（1），boropinalC（2） boropinicAcid（3）,有化合物结构均由核磁共振氢谱，质谱及红外光谱确证，用 X射线衍射法测定了3的晶体及分子结构。     

Total synthesis of the tricyclic marine alkaloids (-)-lepadiformine, (+)-cylindricine c, and (-)-fasicularin via a common intermediate formed by formic acid-induced intramolecular conjugate azaspirocyclization

A very short and efficient enantioselective total synthesis of the tricyclic marine alkaloids (-)-lepadiformine (3), (+)-cylindricine C (1c), and (-)-fasicularin (4) has been developed utilizing the formyloxy 1-azaspiro[4.5]decane 5 as a common intermediate. The key strategic element for the synthesis was the formic acid-induced intramolecular conjugate azaspirocyclization, which proved to be a highly efficient and stereoselective way to rapid construction of the 1-azaspirocyclic substructure of these natural products in a single operation. Thus, the common intermediate 5, synthesized in two steps with 70% overall yield starting from the known (S)-N-Boc-2-pyrrolidinone 7 via the conjugate spirocyclization using an acyclic ketoamide 6, was utilized for the concise and stereoselective total synthesis of (-)-lepadiformine (3), which was accomplished in seven steps with 45% overall yield from 5 (31% yield from 7). The developed strategy based on the conjugate spirocyclization was also applied to the stereoselective total synthesis of (+)-cylindricine C (1c), which was achieved in 10 steps from 5 in 18% overall yield (12% yield from 7). Further application of this approach using 5 led to the synthesis of (-)-fasicularin (4), wherein an extremely efficient method for the introduction of the thiocyanato group via an aziridinium intermediate at the last step was developed. Thus, the highly efficient first enantioselective total synthesis of (-)-fasicularin was accomplished in nine steps with an overall yield of 41% from 5 (28% yield from 7).     

3-羟基-4-甲基-5-乙基-2(5H)-呋喃酮的合成

报道了以草酸二乙酯为原料,制备具有焦糖香味的香料化合物3-羟基-4-甲基-5-乙基-2(5H)-呋喃酮的方法:首先乙基溴化镁与草酸二乙酯通过格氏反应,以约50%产率生成2-氧代丁酸乙酯,然后其在碳酸钾的作用下发生缩合反应,以约94%产率得到3-羟基-4-甲基-5-乙基-5-乙氧羰基-2(5H)-呋喃酮,再通过水解、脱羧反应,得到3-羟基-4-甲基-5-乙基-2(5H)-呋喃酮.路线总收率约36%.     

Route Scouting towards a Methyl Jasmonate Precursor

For the synthesis of methyl jasmonate ( 1 ), via the strategic intermediates 3, 4 , and 6a , we constructed a synthetic network via the diverse intermediates 7 – 10, 13, 14, 17 , and 18 . This allowed us to compare the efficiency of more than 20 novel routes. The most productive pathway with a total yield of 38% is represented by the sequence→ 5a → 5m → 13b → 13a → 6a → 4 and proceeds via sequential bromination, basic elimination, decarbomethoxylation, isomerization, and finally Lindlar hydrogenation. The shortest selective way, 2a →[(E,E)‐ 12b ]→ 3 → 4 , is a two‐pot sequence using a modification of Naef's method, based on an aldol condensation between inexpensive cyclopentanone ( 2a ) and crotonaldehyde, with in situ Corey? Chaykovsky cyclopropanation under phase transfer conditions. The key intermediate 3 was then simply pyrolyzed to afford 4 in 27% total yield. The alternative isomerization method via the six‐step deviation→ 5a → 5c → 8c → 13a → 6a → 4 was longer, although more efficient, with a total yield of 32%. Alternatively, a yield of 34% was obtained via the five‐step sequence→ 5a → 5c → 2h → 2i → 4 . Another favored six‐step pathway,→ 5a → 5c → 2h → 17a → 14a → 4 afforded the target compound in 35% total yield.     

Conjugate addition of amines to chiral 3-aziridin-2-yl-acrylates

Conjugate addition of benzylamine to chiral methyl cis-3-aziridin-2-yl-acrylates was successfully proceeded to yield 3-aziridin-2-yl-3-benzylaminopropionates in high yield with high stereoselectivity. The addition products were used for the asymmetric synthesis of vicinal diamine derivatives including 4-amino-5-methylpyrrolidin-2-one, 3,4-diaminopentanoate, and 5-chloromethyl-4-alkoxycarbonylmethylimidazolidin-2-one.     

Reactions of aromatic and heteroaromatic compounds containing electron-acceptor substituents

Synthetic methods based on accessible furan compounds of 5-benzyl(3-furyl)carbinol, a necessary component for the preparation of modified pyrethrins, were studied. The carbinol was obtained in 24% overall yield by a five-step synthesis starting from 4-bromofuran-2-carboxylic acid, for the preparation of which an improved method is proposed. Acylation of benzene with the chloride of the latter acid gave 4-bromo-2-benzoylfuran (in 77% yield), the reduction of which by the action of AlCl₃ + LiAlH₄ gave 4-bromo-2-benzylfuran (in 74% yield). The latter was treated with butyllithium and dimethylformamide to give 5-benzyl-3-formylfuran, which was converted to the carbinol in quantitative yield by the action of LiAlH₄.See [1] for communication XXI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 306–310, March, 1978.     

相转移催化合成4-{2-[N-甲基-N-(2-吡啶基)]氨基乙氧基}苯甲醛

以2-氯吡啶(1)、2-甲氨基乙醇(2)和4-氟苯甲醛(4)为主要原料,经2步反应合成了4-{2-[N-甲基-N-(2-吡啶基)氨基乙氧基]}苯甲醛(5).第1步反应n(2)∶n(1)=4∶1,反应温度160℃,反应时间约6h,采用减压蒸馏进行后处理,2-[N-甲基-N-(2-吡啶基)氨基]乙醇(3)的收率在93％以上,过量2的回收率在97％以上,回收的2可以重复使用.第2步反应用氢氧化钠做碱性试剂,用甲苯和水分别做为两相的溶剂,在相转移催化剂CTAB作用下进行,经优化后5的收率可达90％以上.2步反应总收率达83％以上.