Synthesis of 16 alpha-hydroxyandrost-4-ene-3,17,19-trione and 3 beta, 16 alpha-dihydroxyandrost-5-ene-17,19-dione; potential intermediates of estriol biosynthesis

16 alpha-Hydroxyandrost-4-ene-3,17,19-trione (10) was synthesized from the 16 alpha-hydroxy-6 beta,19-epoxy-17-one 3 via protection of the 16 alpha-hydroxy function as its tert-butyldimethylsilyl ether or acetate. Reductive cleavage of the epoxy ring of the silyl ether 4 or the acetate 5 with zinc dust gave the 19-alcohol 6 or 7, which was treated with pyridinium dichromate or Jones reagent, respectively, and then hydrolyzed with diluted sulfuric acid, yielding the desired steroid 10. 3 beta,16 alpha-Dihydroxyandrost-5-ene-17,19-dione (14) was also synthesized from 5 alpha-bromo-3 beta,16 alpha-diacetoxy-6 beta, 19-epoxyandrostan-17-one (11) through the intermediates 12 and 13 with the 3 beta- and 16 alpha-hydroxy functions protected as their acetates in a reaction sequence similar to that above.     

C-F or C-H bond activation and C-C coupling reactions of fluorinated pyridines at rhodium: synthesis, structure and reactivity of a variety of tetrafluoropyridyl complexes

Reactions of [RhH(PEt3)3] (1) or [RhH(PEt3)4] (2) with pentafluoropyridine or 2,3,5,6-tetrafluoropyridine afford the activation product [Rh(4-C5NF4)(PEt3)3] (3). Treatment of 3 with CO, 13CO or CNtBu effects the formation of trans-[Rh(4-C5NF4)(CO)(PEt3)2] (4a), trans-[Rh(4-C5NF4)(13CO)(PEt3)2] (4b) and trans-[Rh(4-C5NF4)(CNtBu)(PEt3)2] (5). The rhodium(III) compounds trans-[RhI(CH3)(4-C5NF4)(PEt3)2] (6a) and trans-[RhI(13CH3)(4-C5NF4)(PEt3)2] (6b) are accessible on reaction of 3 with CH3I or 13CH3I. In the presence of CO or 13CO these complexes convert into trans-[RhI(CH3)(4-C5NF4)(CO)(PEt3)2] (7a), trans-[RhI(13CH3)(4-C5NF4)(CO)(PEt3)2] (7b) and trans-[RhI(13CH3)(4-C5NF4)(13CO)(PEt3)2] (7c). The trans arrangement of the carbonyl and methyl ligand in 7a-7c has been confirmed by the 13C-13C coupling constant in the 13C NMR spectrum of 7c. A reaction of 4a or 4b with CH3I or 13CH3I yields the acyl compounds trans-[RhI(COCH3)(4-C5NF4)(PEt3)2] (8a) and trans-[RhI(13CO13CH3)(4-C5NF4)(PEt3)2] (8b), respectively. Complex 8a slowly reacts with more CH3I to give [PEt3Me][Rh(I)2(COCH3)(4-C5NF4)(PEt3)](9). On heating a solution of 7a, the complex trans-[RhI(CO)(PEt3)2] (10) and the C-C coupled product 4-methyltetrafluoropyridine (11) have been obtained. Complex 8a also forms 10 at elevated temperatures in the presence of CO together with the new ketone 4-acetyltetrafluoropyridine (12). The structures of the complexes 3, 4a, 5, 6a, 8a and 9 have been determined by X-ray crystallography. 19F-1H HMQC NMR solution spectra of 6a and 8a reveal a close contact of the methyl groups in the phosphine to the methyl or acyl ligand bound at rhodium.     

Spinosyn g: proof of structure by semisynthesis

[reaction: see text] Spinosyn G was isolated in the late 1980s as a minor component from the broth of our potent, fermentation-derived insecticide spinosad. Its structure was then tentatively identified as 5' '-epispinosyn A (3) on the basis of (1)H and (13)C NMR data, but the 4' '-epi compound 4 could not be conclusively ruled out with the data available. Described herein are unambiguous syntheses of both 3 and 4, whereby 3 was proved identical to the natural product. Compound 4 was prepared from intact spinosyn A by a novel F-TEDA-promoted oxidative deamination to the 4' '-ketone 5, stereoselective reduction to the equatorial alcohol 6, and nitrogen incorporation via the axial azide 7. Compound 3 was obtained by coupling spinosyn A 17-pseudoaglycone (9) with the N-protected dihydropyran 16 derived from methyl l-ossaminide (14). This gave an approximately 2:1 mixture of anomeric products 17 with the desired equatorial glycoside predominating, which was then converted to 3 by N-deprotection and methylation.     

Stabilization of molecular LiF and LiFHF inside metallamacrocyclic hosts

Complexes of molecular LiF and LiFHF were synthesized using the metallamacrocyclic receptors [(cymene)Ru(C(5)H(3)NO(2))](3) (1), [CpRh(C(5)H(3)NO(2))](3) (2), and [CpIr(C(5)H(3)NO(2))](3) (3). LiBF(4) complexes of 1-3 were prepared and subsequently treated with F(-) or FHF(-) to give the desired products in an anion-exchange reaction. All complexes were characterized by multinuclear NMR spectroscopy ((1)H, (13)C, (19)F, (7)Li). Strong scalar coupling between (7)Li and (19)F is observed for the LiF and the LiFHF complexes ((1)J(LiF) = 91-103 Hz). The LiFHF adduct of 1 displays fluxional behavior with fast exchange of the two fluorine atoms. The structures of the complexes 1.LiBF(4), 2.LiBF(4), 1.LiF, 2.LiF, 1.LiFHF, and 3.LiFHF were determined by single-crystal X-ray analysis. Li-F bond lengths between 1.77 and 1.81 A were found. The LiFHF complexes show a hydrogen difluoride anion coordinated in a bent fashion via one fluorine atom to the lithium ion.     

Synthesis of 2-(N-Acetylamino)-2-deoxy-C-glucopyranosyl nucleosides as potential inhibitors of chitin synthases

The C-glucopyranosyl nucleosides (1-4) containing the N-acetyl glucosaminyl and uridine units have been synthesized as nonhydrolyzable substrate analogues of UDP-GlcNAc aimed to inhibit the chitin synthases. The key intermediate, 4-(2'-(N-acetylamino)-3', 4',6'-tri-O-benzyl-2'-deoxy-alpha-D-glucopyranosyl)but-2-enoic acid (5), was prepared from the perbenzylated (N-acetylamino)-alpha-C-allylglucoside (7), by successive oxidative cleavage, Wittig olefination, and ester deprotection. The coupling of the acid 5 with the hydroxyl or amine function of the uridine derivatives (6a or 6b) afforded, respectively, the ester 12 and amide 14. The dihydroxylation of the conjugated double bond in ester 12 or amide 14 was better achieved with osmium tetraoxide/barium chlorate, leading to the expected diols 13 and 15 as a mixture of two diastereoisomers. The desired compounds 1-4 were obtained after catalytic hydrogenation of compounds 12-15.     

Diels-Alder reactions of 4-triflyloxy-2,6,6-trimethyl-2,4-cyclohexadienone. An expedient methodology for the synthesis of bicyclo[2.2.2]oct-5-en-2-ones and bicyclo[2.2.2]octa-5,7-dien-2-ones

The synthesis of 4-triflyloxy-2,6,6-trimethyl-2,4-cyclohexadienone (13), bicyclo[2.2.2]octenones 1a-j and 15a-j, and bicyclo[2.2.2]octadienones 2a-f, 6a-d, and 11a-f is described. The 2,4-cyclohexadienones 4 and 13 were used for the first time as nondimerizing and easily accessible alternatives to 2,6,6-trimethyl-2,4-cyclohexadienone 12 in Diels-Alder reactions with acetylene derivatives 5a-d to prepare the adducts 6a-d and 11a-e in excellent yields. Compounds 11a-d were initially prepared by the alcoholysis of 6a-d to afford bicyclo[2.2.2]octene-2,5-diones 7a-dfollowed by treatment of 7a-d with N-phenyltriflimide in the presence of LHMDS at -78 degrees C. Diels-Alder reaction of 13 with an acetylene equivalent, phenyl vinyl sulfoxide, was also studied. A detailed study of the Diels-Alder reactions of various olefinic dienophiles 14a-j with 13 has been carried out to furnish cycloadducts 15a-j in high yields. Reductive removal of triflyloxy group of vinyl triflates 11a-f and 15a-j was performed in the presence of [Pd(PPh(3))(2)Cl(2)-Bu(3)N-HCO(2)H] to obtain the desired bicyclo[2.2.2]octadienones 2a-f and bicyclo[2.2.2]octenones 1a-j, respectively, in good overall yields.     

Total syntheses of epothilones B and d

A convergent, total synthesis of epothilones B (2) and D (4) is described. The key steps are Normant coupling to establish the desired (Z)-stereochemistry at C12-C13, Wadsworth-Emmons olefination of methyl ketone 28 with the phosphonate ester 8, diastereoselective aldol condensation of aldehyde 5 with the enolate of keto acid derivatives to form the C6-C7 bond, selective deprotection of acid 52, and macrolactonization.     

Syntheses of 1‐(4‐methylsulfonylphenyl)‐5‐aryl‐1,2,3‐triazoles and ‐(4‐aminosulfonylphenyl)‐5‐aryl‐1,2,3‐triazoles

Condensation of 4‐methylsulfonylaniline with aryl aldehyde in ethanol‐tetrahydrofuran afforded the imino compound 3 . 1,3‐Cycloaddtion of diazomethane with compound 3 followed by oxidazation of the triazoline 4 with potassium permanganate gave 1‐(4‐methylsulfonylphenyl)‐5‐aryl‐1,2,3‐triazoles 5 . Similarly, condensation of 4‐(N,N‐dibenzylaminosulfonyl)aniline with aryl aldehyde followed by 1,3‐cycloaddition of diazomethane with the imino compound 11 and the subsequent oxidation of triazoline 12 with potassium permanganate yielded the triazole 13 . Debenzylation of compound 13 with sulfuric acid gave the desired compound 1‐(4‐aminosulfonylphenyl)5‐aryl‐1,2,3‐triazoles 14 .     

Variable strategy toward carbasugars and relatives. 4. Viable access to (4a-carbapentofuranosyl)amines, (5a-carbahexopyranosyl)amines,and amino acids thereof

A chiral, divergent synthesis of two carbafuranosylamines, 1 and 2, two carbapyranosylamines, 3 and 4, two carbafuranosylamino acids, 5 and 6, and two carbapyranosylamino acids, 7 and 8, has been achieved. Highlights of the procedure include the following: a diastereoselective crossed vinylogous Mukaiyama aldol coupling between N-(tert-butoxycarbonyl)-2-[(tert-butyldimethylsilyl)oxy]pyrrole (TBSOP, 9) and 2,3-O-isopropylidene-D-glyceraldehyde (10) for the assembly of the target compound carbon backbone; a high-yielding silylative cycloaldolization that gives the cyclopentanoid and cyclohexanoid motifs; and a reductive or hydrolytic breakage of the lactam C(O)-N link to liberate the carbasugar and install the desired pseudo-anomeric amine and the hydroxymethyl or carboxyl functionalities. The sequences leading to trans-configured carbafuranosyl compounds 1 and 5 and carbapyranosyl compounds 3 and 7 were 12- and 13-step processes, with overall yields of 34%, 35%, 17%, and 16%. Cis-configured isomers 2, 4, 6, and 8 were obtained only in minor yields.     

Synthesis of 3,7-anhydro-D-glycero-D-ido-octitol 1,5,6-trisphosphate as an IP(3) receptor ligand using a radical cyclization reaction with a vinylsilyl tether as the key step. Conformational restriction strategy using steric repulsion between adjacent bulky protecting groups on a pyranose ring

3,7-Anhydro-D-glycero-D-ido-octitol 1,5,6-trisphosphate (5) was designed as a novel IP(3)-receptor ligand having a C-glycosidic structure and was synthesized via a radical cyclization reaction with a temporary connecting vinylsilyl tether as the key step. The phenyl 2-O-dimethylvinylsilyl-3,4, 6-tri-O-benzyl-1-seleno-beta-D-glucopyranoside (7), in the usual (4)C(1)-conformation, was successively treated with Bu(3)SnH/AIBN and under Tamao oxidation conditions to give a mixture of five C-glycosidic products. On the other hand, similar successive treatment of the corresponding 3,4-di-O-TBS-protected substrates 13 and 24, which were in an unusual (1)C(4)-conformaion due to the steric repulsion between the bulky silyl protecting groups, gave the desired 1alpha-C-glycosides 18 and 25, respectively, as the major products. Thus, the course of the radical cyclization was effectively controlled by a change in the conformation of the pyranose ring into a (1)C(4)-form due to steric repulsion between the adjacent bulky TBS-protecting groups at the 3- and 4-hydroxyl groups. From 25, the target 5 was synthesized via phosphorylation of the hydroxyls by the phosphoramidite method. The C-glycoside trisphosphate 5 has significant binding affinity for IP(3) receptor of calf cerebella.     

微波促进下4-乙炔基苯磺酰胺的“一锅法”合成

以3-(4-氯磺酰苯基)-2,3-二溴丙酸和氨水（2.2 eq）为原料,以 DMF为溶剂,经微波辐射25 s,磺酰胺化和脱溴脱羧反应可同步进行,立体选择性地合成中间体(Z)-4-(2-溴乙烯基)苯磺酰胺;该中间体不需分离,直接向反应体系中加入1,8-二氮杂环[5,4,0]十一烯-7 (DBU,2eq),再微波辐射1 min,“一锅法”得到4-乙炔基苯磺酰胺,并通过1H NMR和13C NMR和IR进行了表征,收率达70%。     

对当量为1的预混乙烯/氧气/氩气火焰的实验研究

A comprehensive experimental study of the premixed ethylene/oxygen/argon flame at 2.667 kPa with a stoichiometric equivalence ratio (φ=1) was performed with the tunable synchrotron photoionization and molecular-beam sampling mass spectrometry techniques. The isomers of most observed species in the flame were unambiguously identified by measurements of the photoionization efficiency spectra, e.g. C3H4, C2H4O and C4H4. The mole fraction profiles of species up to C7H8 were measured by scanning the burner position at the selected photon energies near ionization thresholds, and the flame temperature profile was obtained by using Pt/Pt-13%Rh thermocouple. Compared with the previous studies, a lot of new flame species:C3H2, C3H3, C3H5, C2H6O, C4H2, C4H4, C4H6, C3H4O, C3H6O, C3H8O, C5H6, C4H8O and C7H8, were observed. A series of free radicals in the flame are detected to be CH3, C2H3, C2H5, HCO, C3H3 and C3H5.Based on the experimental work, a reduced reaction mechanism was developed including 40 species and 223 reactions. Modeling and measurements agree well for the major species and most intermediates. A detailed kinetic model is desired for this flame.     

Synthetic Studies on Sialoglycoconjugates 15: Synthesis of Ganglioside GM3 Analogs Containing A Variety Of Lipophilic Parts

ABSTRACT

Several ganglioside GM₃ analogs, containing a variety of lipophilic parts in place of the ceramide moiety have been synthesized. Glycosylation of (2S, 3R, 4E)-2-azido-3-0-benzoyl-4-octa-decen-l, 3-diol (2) with 0-(methyl 5-acetamido-4, 7, 8, 9-tetra-0-acetyl-3, 5-dideoxy-o-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-(2, 4-di-0-acetyl-6-0-benzoyl-ß-D-galactopyranosyl)-(l→4)-3-(1)-acetyl-2, 6-di-0-benzoyl-α-D-glucopyranosyl trichloroacetimidate (1) gave the 8-glycoside (5), which was converted, via selective reduction of the azide group, introduction of acyl groups, 0-deacylation, and de-esterification, into the desired compounds (10-12). On the other hand, coupling of 1 with 3-benzyloxycarbonyl-amino-1-propanol (3) or (2RS)-3-benzyloxycarbonylamino-2-0-benzoyl-1, 2-propanediol (4) gave the corresponding ß-glycosides 13 and 14, respectively. These were converted by N-debenzyloxycarbonylation, coupling with 2-tetradecylhexadecanoic acid, 0-deacylation, and hydrolysis of the methyl ester group, into the end products (17 and 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.     

Synthesis and Antimicrobial Activity of Polyfunctionally Substituted Heterocyclic Compounds Derived from 5‐Cinnamoylamino‐2‐Cyanomethyl‐1,3,4‐Thiadiazole

Cinnamoyl isothiocyanate 1 was reacted with 2‐cyanoethanoic acid hydrazide 2 to afford 1‐cyanoacetyl‐4‐substituted thiosemicarbazide 3, which on treatment with a mixture of glacial acetic acid and acetic anhydride gave the desired 5‐cinnamoylamino‐2‐cyanomethyl‐1,3,4‐thiadiazole 4 . Compound 4 was subjected to react with aromatic aldehydes, phenylisothiocyanate, carbon disulphide, and arylidene malononitrile to give coumarin 5 , thiazolidines 8 , 9, and 1,3,4‐thiadiazolo[3,2‐a]pyridine 13 derivatives. The structures of all synthesized compounds were ascertained by spectral and analytical data. Antimicrobial activity of some of prepared compounds was investigated, and compounds 7, 8 were found to exhibit the highest strength.     

5α,11-二羟基-2-氧代桉烷-3-烯的全合成

5α，11-二羟基-2-氧代桉烷-3-(5α-Hydroxy—isopterocarpolone，1)是由贾忠建等于1996年从中药南牡蒿中首次分离得到的一种桉烷型倍半萜类天然产物．桉烷型倍半萜类化合物广泛分布于天然植物中，具有较好的昆虫拒食、抑制细胞繁殖和植物生长调节等多种生理活性．天然产物1的合成研究尚未见报道．     

Solid-phase synthesis of 5-amino-1-(substituted thiocarbamoyl)pyrazole and 1,2,4-triazole derivatives via dithiocarbazate linker

A general method is reported for the parallel solid-phase synthesis of 5-amino-1-(substituted thiocarbamoyl)pyrazole and 1,2,4-triazole derivatives based on the cyclization of polymer-bound dithiocarbazate 3 with various electrophiles, such as 3-ethoxyacrylonitriles 8 and cyanocarboimidates 9. The polymer-bound dithiocarbazate 3, produced by nucleophilic reaction with carbon disulfide and Fmoc-hydrazine on the Merrifield resin, served as the key intermediate for subsequent heterocycle diversification. Further nucleophilic substitution on these polymer-bound 5-amino-1-dithiocarboxypyrazoles 4 and 1,2,4-triazoles 6 with various amines under thermal cleavage condition produced the desired 5-amino-1-(substituted thiocarbamoyl)pyrazoles 5 and 1,2,4-triazoles 7. The progress of reactions could be monitored as polymer-bound intermediates by ATR-FTIR spectroscopy on single bead. The final compounds, obtained in good four-step overall yields and high purities upon cleavage from the resins, were characterized by LC/MS, 1H NMR, and 13C NMR spectroscopy.     

Synthesis of novel 3'-C-methylene thymidine and 5-methyluridine/cytidine H-phosphonates and phosphonamidites for new backbone modification of oligonucleotides

Novel 5'-O-DMT- and MMT-protected 3'-C-methylene-modified thymidine, 5-methyluridine, and 5-methylcytidine H-phosphonates 1-7 with O-methyl, fluoro, hydrogen, and O-(2-methoxyethyl) substituents at the 2'-position have been synthesized by a new effective strategy from the corresponding key intermediates 3'-C-iodomethyl nucleosides and intermediate BTSP, prepared in situ through the Arbuzov reaction. The modified reaction conditions for the Arbuzov reaction prevented the loss of DMT- and MMT-protecting groups, and directly provided the desired 5'-O-DMT- and/or MMT-protected 3'-C-methylene-modified H-phosphonates 1-6 although some of them were also prepared through the manipulation of protecting groups after the P-C bond formation. The modified Arbuzov reaction of 3'-C-iodomethyl-5-methylcytidine 53, prepared from its 5-methyluridine derivative 42, with BTSP provided the 5-methylcytidine H-phosphonate 54, which was further transferred to the corresponding 4-N-(N-methylpyrrolidin-2-ylidene)-protected H-phosphonate monomer 7. 5'-O-MMT-protected 3'-C-methylene-modified H-phosphonates 5, 3, and 7 were converted to the corresponding cyanoethyl H-phosphonates 50, 51, and 56 using DCC as a coupling reagent. One-pot three-step reactions of 50, 51, and 56 provided the desired 3'-C-methylene-modified phosphonamidite monomers 8-10. Some of these new 3'-methylene-modified monomers 1-10 have been successfully utilized for the synthesis of 3'-methylene-modified oligonucleotides, which have shown superior antisense properties including nuclease resistance and binding affinity to the target RNA.     

Versuche zur Synthese von 9β, 10α-Steroiden; B,C,D-tricyclische Verbindungen

In a search for a new and efficient synthesis of the compound 7 , the cyclization of 5 (obtained by a Michael-reaction from 3 and 4 ) was studied. Treatment of 5 with strong acid furnished the known dienedione 8 . Mild acidic conditions gave the bridged alcohol 9 and other, unidentified products, rather than the desired enone 6 . Under basic conditions, 5 did not cyclize to 6 , but underwent retro-Michael reaction. Attempts were then made to convert the dienedione 8 to the 14α-enone 19 . However, both catalytic hydrogenation and lithium-ammonia reduction of 8 yielded mainly 14β-products. In some hydrogenation experiments, isomerization of the dienedione 8 to the phenols 13 (major) and 14 (minor) occurred. The stereochemistry of the new isomeric des-A-androst-9-en-5, 17-diones ( 16, 17 and 20 ) was determined by chemical and spectroscopic methods.     

Enantiospecific synthesis of annulated nicotine analogues from D-glutamic acid. 7-Azabicyclo[2.2.1]heptano[2.3-c]pyridines

The conformationally restricted nicotinoid (1S,4S)-7-methyl-7-azabicyclo[2.2.1]heptano[2,3-c]pyridine dihydrochloride has been prepared enantiospecifically from D-glutamic acid. The method involved a lithium cis-2,6-dimethylpiperidide-mediated intramolecular anionic cyclization of (2S,5R)-N-(tert-butyloxycarbonyl)-5-[3-(4-N-chloropyridinyl]proline methyl ester in tandem with a standard decarboxylation sequence. Reductive amination afforded the desired N-methylated [2.2.1]bicyclonicotinoid. Cyclization of the corresponding iodopyridinylproline methyl ester, obtained via ultrasound-facilitated chloro-iodo exchange, was also effected.