Synthetic transformation of ptychantin into forskolin and 1,9-dideoxyforskolin

Forskolin (1), a highly oxygenated labdane diterpenoid and an activator of adenylate cyclase, has been synthesized in 12 steps and 12% overall yield from ptychantin A (4), which has been isolated from liverwort Ptychanthus striatus in good yield. The 1alpha-hydroxy group was furnished by stereoselective reduction of the corresponding carbonyl group by sodium in t-BuOH. The 9alpha-hydroxy group was introduced stereoselectively by epoxidation of delta(9.11)-enolether. 1,9-Dideoxyforskolin (2), an inhibitor of glucose transporter, has been synthesized in 8 steps and 37% overall yield. The hydroxy group at C-1 was removed by solid-state thicarbonylimidazolation and subsequent radical cleavage.     

Synthesis and polymerization of sterically hindered 2,5-diphenyl- and 2,3,5-triphenyl-1-vinylpyrroles

Sterically hindered 2,5-diphenyl-and 2,3,5-triphenyl-1-vinylpyrroles have been obtained by the vinylation of the corresponding NH-pyrroles with acetylene in superbasic catalytic system KOH—DMSO in up to 78% yield. 2,3,5-Triphenyl-1-vinylpyrrole has also been obtained in 75% yield by the regioselective bromination of 2,3-diphenyl-1-vinylpyrrole with subsequent cross-coupling of 5-bromo-2,3-diphenyl-1-vinylpyrrole with phenylmagnesium bromide in the presence of dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II). 2,5-Diphenyl- and 2,3,5-triphenyl-1-vinylpyrroles undergo a free-radical polymerization (AIBN, 80 °C) to form oligomers in 11 and 27% yield, respectively.     

Dakin反应的研究

本文对九个酚醛及酚酮类化合物的Dakin反应进行了研究。由于避免了过度的氧化和副反应,所以产率较文献报道的60～80％要高,可达81～96％。其中,2-甲酰基雌酚酮和4-甲酰基雌酚酮的Dakin反应尚未见报道,产率几乎是计算量的。采用本文的方法,可将Dakin反应由通常的甲酰基或乙酰基成功地扩展应用到含丙酰基的酚酮。     

Methane coupling in microwave plasma under atmospheric pressure

Methane coupling in microwave plasma under atmospheric pressure has been investigated.The effects of molar ratio n(CH4)/n(H2),flow rate and microwave power on the reaction have been studied.(1)With the decrease of n(CH4)/n(H2)ratio,methane conversion,C2 hydrocarbon yield,energy yield and space-time yield of acetylene increased,but the yield of carbon deposit decreased.(2)With the increase of microwave power,energy yield of acetylene decreased,but space-time yield of acetylene increased.(3)With the increase of flow rate,energy yield and space-time yield of acetylene increased first and then decreased.Finally,under the reaction conditions of CH4 flow rate of 700 mL/min,n(CH4)/n(H2)ratio of 1/4 and microwave power of 400 W,the energy yield and space-time yield of acetylene could reach 0.337 mmol/kJ and 12.3 mol/(s m3),respectively.The reaction mechanism of methane coupling in microwave plasma has been investigated based on the thermodynamics of chemical reaction.Interestingly,the acetylene yield of methane coupling in microwave plasma was much higher than the maximum thermodynamic yield of acetylene.This phenomenon was tentatively explained from non-expansion work in the microwave plasma system.     

Cyclopropane-annelated azaoligoheterocycles by Ti-mediated intramolecular reductive cyclopropanation of cyclic amino Acid amides

Starting from pyrrole- and indole-2-carboxylic acids 5 a and 5 b, the tri- and tetracyclic N,N-dibenzylcyclopropylamines 7 a and 7 b have been synthesized in 52 and 33 % overall yield, respectively. The synthesis of the enantiopure tetracyclic diamine 10 has been achieved applying the established set of reactions to N-tert-butoxycarbonylindoline-2-carboxylic acid (8) in 46 % overall yield. The amide 15 could not be prepared in the same way starting from the N-tert-butoxycarbonylproline 11. In fact, in the allylation step the stereogenic center was deprotonated and the doubly alkylated amide 13 was formed. However, the desired intermediate 15 could be obtained from L-proline in 49 % yield performing first the N-allylation step, then the introduction of the amide function. From 15, the cyclopropane-annelated pyrrolizidine 16 was obtained in 70 % yield as a mixture of (1aS,6aS,6bR)-16 and (1aR,6aS,6bS)-16 diastereoisomers in a ratio of 1:2.9.     

Efficient and selective synthesis of siphonarienolone and related reduced polypropionates via Zr-catalyzed asymmetric carboalumination

[reaction: see text] Siphonarienolone (1) has been synthesized from siphonarienal (3) in 66% over four steps. Synthesis of 3, in turn, has been achieved in two steps (85% combined yield) from 4, prepared from 3-buten-1-ol in seven steps (23% combined yield). Also, a two-step conversion of 3 into siphonarienone (2) is reported.     

Regioselective quinazolinone-directed ortho lithiation of quinazolinoylquinoline: practical synthesis of naturally occurring human DNA topoisomerase I poison luotonin a and luotonins B and E

A regioselective quinazolinone-directed ortho lithiation on an adjacent quinoline moiety has been used as a key step for a short, efficient, and practical synthesis of the human DNA topoisomerase I poison luotonin A and luotonins B and E. The quinazolinoylquinoline 5 on treatment with in situ-generated nonnucleophilic mesityllithium furnished the desired dilithiated intermediate 6, which on treatment with formaldehyde followed by Mitsunobu ring closure reaction gave luotonin A (1a) in very good yield. The reaction of dilithiated intermediate 6 with DMF directly furnished luotonin B (1b) in 81% yield. Luotonin B (1b) on methylation with p-TSA/methanol gave luotonin E (1c) in 82% yield.     

PHOTOINTERACTION OF BENZOPHENONE TRIPLET WITH LYSOZYME

The quenching of the benzophenone triplet by lysozyme and its constituent amino acids in aqueous solutions have been studied. Native lysozyme quenches the benzophenone triplet with a high rate constant, 4 x 10(9) M-1 s-1. The quenching process takes place with production of significant amounts of free ketyl radicals, phi ketyl = 0.56, but with a very low benzophenone consumption yield (0.022). The consumption yield is considerably smaller than that observed for the free amino acids. This difference can be explained in terms of a dominant back hydrogen transfer to the protein in the disproportionation of the free radicals produced. Reduced and carboxymethylated lysozyme shows a higher quenching rate (7.8 x 10(9) M-1 s-1) and a larger benzophenone consumption yield (0.07). The deactivation of the benzophenone triplet by the native protein leads to its inactivation, with a quantum yield of 0.01. Tryptophan and arginine residues are destroyed with a quantum yield of 0.01. In the modified enzyme tyrosine and methionine groups are also consumed.     

New building block for polyhydroxylated piperidine: total synthesis of 1,6-dideoxynojirimycin

(3R,4S)-3-Hydroxy-4-N-allyl-N-Boc-amino-1-pentene 10, an important precursor for the synthesis of polyhydroxylated piperidines, has been achieved as a single diastereomer without racemization via vinyl Grignard addition to N-Boc-N-allyl aminoaldehyde 9, which was derived from an enantiopure natural amino acid. Having forged a tetrahydropyridine ring scaffold 13 from 10 in 85% yield via RCM using Grubbs II catalyst, we were able to effect its stereodivergent dihydroxylation, via a common epoxide intermediate to yield a range of interesting hydroxylated piperidines, including ent-1,6-dideoxynojirimycin (ent-1,6-dDNJ) 1 (28% overall yield) and 5-amino-1,5,6-trideoxyaltrose 2 (29% over all yield) in excellent dr. To the best of our knowledge, our synthesis of ent-1,6-dDNJ 1 is the most expeditious to date.     

Performance improvement of a PGNAA setup due to change in moderator design: A Monte Carlo study

Effect of neutron source-moderator geometry has been studied on the performance of a thermal neutron capture-based prompt gamma neutron activation analysis (PGNAA) setup. In the study prompt gamma-ray and thermal neutron yield was calculated for various positions of the neutron source inside 3–10 cm long high density polyethylene moderators. The study has been carried out for a Portland cement sample using Monte Carlo calculations. The maximum yields of the thermal neutrons and prompt gamma-rays have been observed for a neutron source at a distance of 1 cm from the sample. The maximum yield of the 1.94 and 6.42 MeV prompt gamma-ray from a Portland cement sample has been observed for moderators having length equal to or greater than 7 cm. The yield of both gamma rays is 2.57 times higher than the previously reported value for a PGNAA setup with the source placed outside a 5 cm thick moderator. The higher yield of gamma rays will result in higher sensitivity of the PGNAA setup.     

Synthesis of novel retinoid X receptor-selective retinoids

Retinoids 1-5 have been identified as potent RXR agonists for evaluation in the treatment of non-insulin-dependent (type II) diabetes mellitus (NIDDM). Highly convergent syntheses of 1-5 have been developed. The core tetrahydronaphthalene 7, employed in the synthesis of 1 and 2, was prepared in 98% yield using an AlCl(3)-catalyzed (0.03 equiv) Friedel-Crafts alkylation of toluene with 2,5-dichloro-2,5-dimethylhexane 6. A nitromethane-mediated Fridel-Crafts acylation of 7 with chloromethylnicotinate 9 was developed to prepare ketone 10 in 68% yield. Chelate-controlled addition of MeMgCl to 10 followed by dehydration afforded olefin 11 in 65% yield. Cyclopropanation of 11 with trimethylsulfoxonium ylide, followed by saponification, completed a five-step synthesis of 1 in 33% yield. FeCl(3)-catalyzed (0.05 equiv) Friedel-Crafts acylation of 7 with chloromethylterephthalate 14 afforded ketone 15 in 81% yield. Saponification of 15 and reaction with 50% aqueous NH(2)OH in AcOH afforded a 9:1 mixture of cis and trans oximes, from which the desired cis-oxime 2 was isolated in 43% yield. The core bromo-dihydronaphthalene 29 required for the synthesis of 3-5 was prepared by a Shapiro reaction. Transmetalation of 29 and reaction with Weinreb amides 30b or 36 afforded ketones 32 and 37, which were converted into 3-5 using chemistry comparable to the tetrahydronaphthylene series. Suzuki coupling of boronic acids 41 and 42 with vinyl triflate 43 provided an alternative approach to the synthesis of this class of compounds.     

Photochemistry of imidazolides II. C2-C3 cleavage of carboxylic acid chains. A convenient new method for the side-chain degradation of bile acids and of lanosterol.

Irradiation of N-stearoylimidazole ( 1 ) gave hexadec-1-ene ( 4 ) in 45% yield, whereas irradiation of N-(4-methylstearoyl)imidazole ( 13 ) possessing a tertiary hydrogen atom γ to the carbonyl group led to 2-methylhexadec-1-ene ( 14 ) in 62% yield. These results are explained by a two-stage process: acyl migration, followed by Norrish Type II eliminatior. The reaction has been utilized for the side chain degradation of bile acids and of lanosterol, in which the second stage of the reaction was shown to proceed in up to 70% yield.     

Alcoholysis and aminolysis of Di-and trithioester chain-transfer agents of free-radical polymerization

The alcoholysis and aminolysis of (S)-1-phenylethyl-(O)-ethyl dithioxanthate, 1-phenylethyl dithiobenzoate, and bis(1-phenylethyl) trithiocarbonate have been studied. These compounds model end groups of polystyrenes prepared by the controlled radical polymerization carried out in the presence of di-and trithioesters. It has been shown that the yield of 1-phenylethylthiol is markedly dependent on the structure of ester. Possible mechanisms governing side reactions are considered, and conditions providing the quantitative yield of polystyrenes with end thiol groups have been estimated.     

Synthesis and rearrangement of [1,1′-bicyclobutyl]-1-ols and spiro[3.4]octan-5-ols: a general access to bicyclo[3.3.0]octenes (hexahydropentalenes)

Several new Grignard reagents based on substituted cyclobutanes have been generated and added to cyclobutanones to yield mono- to trimethylated [1,1′-bicyclobutyl]-1-ols. Mono- to trimethylated spiro[3.4]octan-5-ols have been prepared from the parent ketone via alkylation and/or addition reactions. Upon treatment with acid, all [1,1′-bicyclobutyl]-1-ols and spiro[3.4]octan-5-ols rearrange to yield a single bicyclo[3.3.0]octene.     

An Improved Preparation of Ethyl 2-Oxo-3-Pyrrolidinecarboxylate

The title 3-substituted pyrrolidinone is a useful building block that has been prepared via base-catalyzed additions of diethyl malonate to 1-benzene-sulfonylaziridine (3 steps, 43% overall yield),¹ 1-iodo-2-azidoethane with subsequent reduction and cyclization (49% yield for 5 steps from commercially available materials),² or chloroacetonitrile with a subsequent Raney Ni reduction (15% overall yield).³ We now wish to report a simple two step process that gives good yields of the title compound.     

Highly selective deblocking of propargyl carbonates in the presence of propargyl carbamates with tetrathiomolybdate

Propargyloxycarbonyl chloride, 1, has been used to protect the hydroxyl and amino functionalities of amino alcohols and aminophenols in one pot using triethylamine or pyridine as a base. The increased reactivity of benzyltriethylammonium tetrathiomolybdate, 2, toward propargyl carbonates over propargyl carbamates is studied in detail and has been exploited further to develop an orthogonal protection strategy for the hydroxyl and amino functionalities. For example, 2-amino-1-butanol, 6a, was treated with 1 to get the N,O-diPoc compound 7a in 90% yield, which when treated with 1.1 equiv of 2 at room temperature removes the Poc group attached to oxygen while leaving the one attached to nitrogen intact to yield compound 8a in 85% yield. This particular observation offers a new protecting strategy where an amine and an alcohol group can be protected simultaneously in one pot, and in a later synthetic step, if the alcohol group has to be deprotected selectively, it can be achieved with 1 equiv of 2.     

Gamma radiation induced graft copolymerization of acrylamide onto EPDM blended with PE

Gamma radiation induced grafting of acrylamide (AAm) onto vulcanized strips of EPDM and EPDM/PE blends has been carried out. The effects of different parameters on the graft yield have been investigated. These parameters include: radiation dose, monomer concentration, diluent composition and types of inhibitors. It has been found that water is the most appropriate solvent. The preswelling of crosslinked rubber samples in cyclohexane prior to grafting enhances the grafting and the addition of methanol to water as binary diluent in the ratio (1 : 1) decreases the graft yield. The presence of Mohr's salt and copper sulfate in the reaction mixture in the molar ratio (2.1 : 0.5) markedly increases the graft yield. Evidence of grafting have been conducted using thermal analysis as well as swelling measurements in water. Also, it has been found that the mechanical properties of the blends decrease at graft yield 13%. Copyright © 2002 John Wiley & Sons, Ltd.     

THE FLAVIN-SENSITIZED PHOTOOXIDATION OF NUCLEOTIDES — III. THE PARTICIPATION OF OXYGEN

Abstract— Quantum yields for the lumiflavin-sensitized oxidation of guanosine monophosphate and adenosine monophosphate in solution have been measured as functions of oxygen and nucleotide concentration. The quantum yield increases with oxygen concentration at low oxygen concentrations, but quenching of the excited flavin molecule by oxygen results in a fall in quantum yield at higher concentrations. It has also been established that the reciprocal of the quantum yield is linearly related to the reciprocal of the nucleotide concentration. A mechanism in which molecular oxygen reacts with an excited complex formed between triplet lumiflavin and the nucleotide is consistent with these observations.
A value for the second-order rate constant for the quenching of triplet lumifiavin by oxygen of 2·65 × 10⁹ M ^-1 sec^-1 has been obtained.     

Structure revision and syntheses of epohelmins A and B

[structures: see text] Epohelmins A (24) and B (26) have been reassigned as pyrrolizidin-1-ols, rather than the proposed 9-oxa-4-azabicyclo[6.1.0]nonane structures 1 and 2, respectively. Syntheses of epohelmin A (24) (eight steps, 52% overall yield) and epohelmin B (26) (11 steps, 43% overall yield) have been achieved starting from N-Cbz-(S)-prolinal (9) and ortho ester ketone 17 using a stereoselective aldol reaction and a stereoselective reductive cyclization as the key steps.     

Simple syntheses of (±) -β-copaene, (±) -β-ylangene and lemnalol.

The ketone 1a, which we have prepared from geranylacetone in 38% yield by a four step sequence, has been converted to β-copaene and β-ylangene by a three step sequence. Oxidation of β-ylangene with SeO₂ gives lemnalol in 76% yield.