FIRST SYNTHESIS OF(±)-3-[(5-HYDROXY)HOMOGERANYL]-△~2-BUTENOLIDE

ＦＩＲＳＴＳＹＮＴＨＥＳＩＳＯＦ（±）－３－［（５－ＨＹＤＲＯＸＹ）ＨＯＭＯＧＥＲＡＮＹＬ］－△￣２－ＢＵＴＥＮＯＬＩＤＥ￥ＪｉｎＱＵ；ＷｅｉＤｏｎｇＬＩ；ＪｉｎｇＬＩ；ＹｕＬｉｎＬＩ（ＳｔａｔｅＫｅｙＬａｂｏｒａｔｏｒｙｏｆＡＰＰｌｉｅｄＯｒｇａｎ...     

STUDIES ON THE SYNTHESIS OF(±)-CEMBRENE-A

A precursor 2 of cembrene-A(a termite trail pheromone)was prepared fromgeraniol through 7 steps.     

EASY SYNTHESIS OF 1-ALLYL-1-DEOXY-β- AND α- d-LYXOFURANOSES

2,3;5,6-Di-O-isopropylidene-α-d-mannofuranosyl chloride reacted with allylmagnesium bromide with preferential inversion of the anomeric configuration to furnish a mixture of the 1-allyl-1-deoxy-β- and α-d-mannofuranoses. Separation of β and α derivatives was possible only after conversion to the 1-allyl-1-deoxylyxofuranoses 2 and 3. The β configuration of the predominant product 2 was proved using the NOE method.     

STUDIES ON THE SYNTHESIS OF THE SPIROKETAL FRAGMENT OF AZADIRACHTIN(Ⅰ)

The stereoselective synthesis of substituted [2,2,1]-bicyclo-heptan-2-one 12,a supposed intermediate to the spiroketal fragment of azadi-rachtin was described.When 12 was treated with mCPBA in CH_2Cl_2 in the pres-ence of excess amount of solid sodium bicarbonate,only 13 was obtained.Thespiroketal intermediate 20 was converted from 9 through 5 steps by an alterna-tive route.     

STUDIES ON THE TOTAL SYNTHESIS OF MAYTANSINOIDS (Ⅳ)——SYNTHESIS OF MAYTANSINE

This paper reports the total synthesis of optically pure maytansinol and maytansine. The physical constants and spectral data including R_f, m.p., specific rotation, HPLC, UV, CD, IR, NMR, and MS, of synthetic maytansinol and maytansine are identical with those of natural products in all respects. The preliminary biological test showed that synthetic maytansine possesses the same inhibitory activity in vitro against carcinoma cells as the natural product.     

SYNTHESIS AND CATIONIC RING-OPENING POLYMERIZATION OF 1, 4-ANHYDRO-2, 3-DI-O-(P-AZIDOBENZYL)-α-D-RIBOPYRANOSE

New highly stereoregular 2, 3 -di- O-(p-azidobenzyl )-(1 →5 ) - α-D -ribofuranan was synthesized byselective ring-opening polymerization of 1, 4-anhydro-2, 3 - di-O -(p-azidobenzyl )-α-D -ribopyranose(ADABR) using phosphorus pentafluoride or tin tetrachloride as catalyst at low temperature indichloromethane. The monomer was obtained by the reaction of p - bromomethyl -phenyleneazide with 1, 4 -anhydro-α-D-ribose in DMF. The structure of poly(ADANR) was identified by specific rotation and ~(13)C-NMR spectroscopy. Acid chloride-AgCl_4 complex catalyst such as CH_2=C(CH_3)C~+OClO_4~- used in thepolymerization resulted in polymers with mixed structures, i.e. (1→5)-α-D-ribofuranosidic and (1→4)-β-D-ribopyranosidic units. However, with C_6H_5C~+OClO_4~- as catalyst, pure (1→5)-α-D-ribofuranan was obtained.The effects of catalyst, polymerization temperature and time on polymer stereoregularity were examined, andthe mechanism of the ring-opening polymerization was discussed.     

STUDIES ON THE SYNTHESIS OF TRACHYLOBAGIBBERELLINANALOGUE(Ⅱ)SYNTHESIS OF DIMETHYLESTER OF 3-HYDROXY-△1_10-12,16-CYCLOGIBBERELLIN 12

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RECENT IMPROVEMENTS TOWARDS THE SYNTHESIS OF THE C-GLUCURONOSYL CANCER CHEMOPREVENTIVE (β-d-GLUCOPYRANOSYLURONATE)-4-RETINAMIDOPHENYLMETHANE

Evidence suggests that the glucuronide conjugates of retinoids may be active metabolites of the parent compounds with potential utility as drugs.¹ We have recently shown that the O-glucuronide metabolite 1 of the synthetic retinoid N-4-hydroxyphenylretinamide (2) shows reduced toxicity and a significant chemopreventive advantage relative to the parent retinoid in a carcinogen-induced rat mammary cancer model.² In efforts to determine whether these conjugates function as intact molecules or must be hydrolyzed back to 2, we designed and synthesized a series of C-glycosyl and C-glucuronosyl analogues of 1 ³. Our syntheses of these compounds are lengthy (10-12 steps) and lead to the desired products in less than 4% overall yields. Limitations on the availability of these compounds led us to evaluate them using a modified protocol for the carcinogen-induced rat mammary tumor model. While many of our analogues showed cancer chemopreventive activity in this assay, C-glucuronosyl analogue 3 has proven to be the most effective analogue of 2 we have yet evaluated in this model.⁴ Unfortunately, compound 3 was prepared in the poorest overall yield among these analogues. However, its potent activity and low toxicity make it an important candidate for expanded biological studies. Because additional studies of this important new compound will benefit from improvements in its synthesis, we briefly describe below recent dramatic improvements we have made in the preparation of 3.     

SYNTHESIS OF α-AMINO-β-(4-IMIDAZOLYL)-ETHYLPHOSPHONIC ACID,THE PHOSPHONOISOSTERE OF HISTIDINE

A short synthesis starting from 4-imidazolylmethanol(2)was developedfor the phosphonoisostere of histidine,-amino-β-(4-imidazolyl)-ethylphosphosphonic acid,His(P)(1).The synthesis features Wittig-Hornerreaction of aldehyde(4)with diphosphonate(5)followed by selectivedetritylation with 50% formic acid.     

INVESTIGATION ON SYNTHESIS, STRUCTURE AND PROPERTIES OF THE CLUSTER COMPLEX,[(MoS_4)Fe(MoS_4O)] [(C_4H_9)_4N]_3

In this paper, we report a new Mo-Fe-S cluster complex containing an oxygen ligand. Itwas synthesized by the reaction of (NH_4)_2 MoS_4, FeCl_3 in the solution of sodium glycol. The chemical formula of the crystal, [(MoS_4) Fe (MoS_4O)] [(C_4H_9)_4N]_3, was characterized byX-ray. This complex was determined by IR, UV/Vis and Mossbauer spectra as well. The re-suits from Mossbauer spectra of the complex show an isomer shift, δ_m = 0.2263mm/s and aquadrupole splitting, E_q = 0.4527mm/s. The complex has some activity for the reduetion of aectylene to ethylene in the presenceof KBH_4.     

THE CRYSTAL AND MOLECULAR STRUCTURE OF THE VIOLET ISOMER OF (⊘P)2[(CF3)2C2S2] RuCO

Abstract

The crystal structure and the details of the molecular configuration of the violet isomer of (?₃ P)₂ [(CF₃)₂ C₂ S₂] -RuCO were established from three dimensional, single crystal, X-ray diffraction data. This isomer crystallizes in the orthorhombic system, space group D¹⁵ ₂h-Pbca, in a cell whose dimensions are: a = 22.394(8), b = 19.107(6) and c = 17.480(5)Å. The measured and calculated densities are 1.56(2) and 1.56 gm-cm^?3 and z = 8 molecules/ unit cell. The shape of the polyhedron of ligands around the central Ru atom is a square pyramid distorted principally by the fact that the Ru—C bond length is shorter than the four bonds to the nearly equidistant phosphorus and sulfur ligands. The dithiolene sulfur atoms occupy adjacent positions in the basal plane; the two triphenylphosphine ligands occupy a basal plane site and the unique axial position while the carbonyl carbon occupies the fourth basal plane site.

The two Ru—S bond lengths are 2.298(3) and 2.287(3) Å, while the two Ru—P distances are 2.353(3) and 2.274(3) A in length, the latter being the basal plane Ru—P bond. The Ru—C and C—O bond lengths are 1.849(11) and 1.133(11) Å, respectively. The bonds within the triphenylphosphines are normal and the phenyl rings are planar, nearly equilateral hexagons. The dithiolene ligand has C—S and (ethylene C)—(ethylene C) distances of 1.719(10) and 1.358(12) Å, respectively, which conform more closely to values expected from an unsaturated cis-dithiol than a dithioketone. The closest inter or intramolecular contact between the Ru atom and the phenyl hydrogens is 3.08 A, which is about 0.5 Å longer than the sum of van der Waals' radii. When refinement was complete, the unweighted and weighted R(F) factors, for 2386 observed reflections, were 0.060 and 0.055, with an error of fit of 1.16.     

SYNTHESIS OF 3-(2-QUINOLYL)TROPOLONES

3-Acetyltropolone was reacted with 2-aminobenzaldehydes to afford 3-(2-quinolyl)tropolones.2-Acetyl-7-methylaminotropone and 2-acetyl-7-ethylamino-tropone were respectively reacted with 2-aminobenzaldehydes to give the corres-ponding 2-(2-quinolyl)-7-methylaminotropones and 2-(2-quinolyl)-7-ethylaminotro-pones,which after treatment with sodium hydroxide solution also afforded 3-(2-quinolyl)tropolones.     

SYNTHESIS OF DERIVATIVES OF 3-β-D-XYLOPYRANOSYL-1,2,4-OXADIAZOLES

The synthesis of derivatives of 3-β-D-xylopyranosyl-1,2,4-oxadiazolesis accomplished by condensing protected β-D-xylopyranosyl amidoxime with acidanhydrides or various substituted benzoyl chlorides in good yield.Thestructures of now derivatives were identified by spectra and elemental analysis.The stability of 1,2,4-oxadiazole ring and mechanism of cyclization were.investigated.     

STUDY ON ASYMMETRIC SYNTHESIS OF 19-NORSTEROIDS SYNTHESIS OF A NEW OPTICALLY ACTIVE SYNTHON, (2R, 3S)-( )-2-ETHYL-2-(3'-OXO-4'-ENE)-AMYL-3-ACETOXY-CYCLOPENTANONE

This paper reports the synthesis of a new optically active synthon 6 for the asymmetricsynthesis of 19-norsteroids. Symmetric trione 9 obtained by the reaction of γ-carbonyl sulfo-xide 12b with 2-cthyl-1, 3-cyclopetanedione 8, was reduced asymmetrically by Saccharomycescerevisiae to (2R,3S)-(-)-14 and subsequently transformed into (2R,3S)-( )-6 by a shortreaction sequence. The absolute configuration of the asymmetrical product, (2R, 3S)-(-)-14,was established by converting it into the known compound (2R, 3S)-( )-17.     

STUDIES ON THE SYNTHESIS OF D-GLUCURONIC ACID DERIVATIVES OF 2-BUTOXY-5-FLUORO-3H-4-PYRIMIDONE AND THEIR ANTICANCER ACTIVITIES

2-Butoxy-5-fluoro-3H-4-pyrimidone derivatives of D-glucuronic acid having0-glycosidic linkage or N-glycosidic linkage were synthesized and their anticanceractivity tested.Their structures were confirmed by elementary analysis,IR spectraand ~1HNMR.     

XPS STUDY ON THE ROLE OF CO_2 IN LOW-PRESSURE METHANOL SYNTHESIS

Surface characterization of CuO-ZnO-Al_2O_3 catalysts for low pres-sure methanol synthesis was carried out by using X-ray photoelectron spec-troscopy(XPS)combined with reaction chamber under simulated industrialoperating condition.Under the reduction and reaction conditions,no stableCu~(2+) or Cu~+ ions were found,only Cu~0 species was detected.ZuO could be re-duced with result of forming oxygen-deficient structure ZnO_x(X<1)andoxygen vacancy on the surface.The presence of enough amount of CO_2 infeed gas enhanced copper dispersion.It is believed that highly dispersed Cu~0 in intimate contact with ZnO is one of the active components for methanol syn-thesis and the optimal structure of the active unit is Cu——Zn—O(“□”is oxygen vacancy).It is proposed that the main role of CO_2 is to establish anoxidation potential of syngas so as to accelerate the oxidation-reduction cyclebetween Cu~0 and Cu~(δ+)/or Cu~+ during methanol synthesis as well as to preventCu~0 crystallites from aggregating and thus to maintain the catalyst in high ac-tivity and have long life.     

SYNTHESIS OF 2′-DEOXY-2′-FLUORO- 1-β-d-ARABINOFURANOSYL URACIL DERIVATIVES: A METHOD SUITABLE FOR PREPARATION OF [18F]-LABELED NUCLEOSIDES

ABSTRACT

N-glycosylation of 2,4-bis-O-(trimethylsilyl)-pyrimidine bases with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-1-(Br, OBz)-α-d-arabinose derivatives are reported. 1-Bromo-arabinose provides high yield and a favorable anomeric ratio (β/α) of pyrimidine nucleoside in either MeCN or CH₂Cl?CH₂Cl. This method should be suitable for the synthesis of 2′-deoxy-2′-[¹⁸F]fluoro-1-β-d-arabinofuranosyluracil derivatives.     

STUDIES ON THE PRENYLELAVONOIDS PART Ⅵ SYNTHESIS OF (±)-AMORITIN

ＳＴＵＤＩＥＳＯＮＴＨＥＰＲＥＮＹＬＥＬＡＶＯＮＯＩＤＳＰＡＲＴⅥＳＹＮＴＨＥＳＩＳＯＦ（±）－ＡＭＯＲＩＴＩＮＬｉａｎＹｕｎＺＨＡＯ；ＦａｎｇＪｉｅＺＨＡＮＧ；ＹｕＬｉｎＬＩ（ＳｔａｔｅＫｅｙＬａｂｏｒａｔｏｒｙｏｆＡｐｐｌｉｅｄＯｒｇａｎｉｃＣｈ...     

SYNTHESIS OF 4-SUBSTITUTED (OR 4-SPIRO) 3-OXABICYCLO[3.1.0]HEXAN-2-ONE

Cyclopropanedicarboxylic anhydride can be converted to 4-substituted (or 4-spiro-)3-oxabicyclo[3.1.0]hexan-2-one by addition of Grignard (or α,ω-di-Crignard) reagents in ether or tetrahydrofuran solution.