The protection of uracil and guanine residues in oligonucleotide synthesis

The protection of uracil and 2-$\text{N}$-acyl guanine residues with 4-$\text{O}$-phenyl [or 4-$\text{O}$-(2,4-dimethylphenyl)] and 6-$\text{O}$-(2-nitrophenyl) groups as in $\text{7a}$ [or $\text{7b}$] and $\text{9}$, respectively, is described. These $\text{O}$-aryl protecting groups, which appear to withstand the usual conditions of oligonucleotide synthesis, may readily be removed by treatment with 2-nitrobenzaldoximate ions.     

A new cytokinin from the fruits of zantedeschiaaethiopica

A new purine derivative with cytokinin activity was isolated from the cuckoo-pint fruits ($\text{Zantedeschia}$$\text{aethiopica}$) and identified as 6-(o-hydroxybenzylamino)-2-methylthio-9-β-D-glucofuranosylpurine $\text{1}$.     

Conformational dependence of pyranoid rings 1,2-cis-fused to dioxolane rings on the configuration of the dioxolane rings in acetylated derivati

X-Ray and ¹H N.M.R. studies on pyranoid rings 1,2-$\text{cis}$-fused to dioxolane rings in acetylated $\text{D}$-gluco- and $\text{D}$--galactopyranose derivatives demonstrate that the configuration of the dioxolane ring influences the conformation of the pyranoid ring in the $\text{D}$-gluco but not in the $\text{D}$-galactopyranose series. The crystal structure of 3,4,6-tri-$\text{O}$-acetyl-1,2-$\text{O}$-(R)--(l-cyano-ethylidene)-α-$\text{D}$-glucopyranose ($\text{1}$) and 3,4,6-tri-$\text{O}$-acetyl-1,2-$\text{O}$-($\text{R}$)-(1-cyano-ethylidene)-α-$\text{D}$-galactopyranose ($\text{2}$)have been determined by X-ray analysis. Lattice parameters for $\text{1}$ are a=20.6021 (11), b=8.0438 (2), c=5.5541 (1) Å and β= 95.588 (3)° for a cell with P21 symmetry. These parameters for $\text{2}$ are a=20.3361 (7), b=10.0907 (2), c=18.9115 (5) Å, β =112.399 (2)°, C2, with two crystallographycally independent molecules. The conformation of the pyranoid ring in both compounds can be described as flattened ⁴C₁ and that of the dioxolane ring as distorted E₁. The importance of the torsion angles for describing problems of configuration is remarked and the use of relative configurational angles is stressed. The ¹H N.M.R. spectra of $\text{1}$ and $\text{2}$ and 3,4,6-tri-$\text{O}$-acetyl-1,2-O-(S)- and (R)-ethylidene-α-$\text{D}$-glucopyranose ($\text{5}$ and $\text{7}$), 3,4,6-tri-O-acetyl--1,2-O-(S)- and ($\text{R}$)-ethylidene-α-$\text{D}$-galactopyranose ($\text{6}$ and $\text{8}$), and 3,4,6-tri-$\text{O}$-acetyl-1,2-$\text{O}$-($\text{S}$)-and ($\text{R}$)-benzylidene-α-$\text{D}$-glucopyranose ($\text{9}$ and $\text{10}$) have been analyzed by using iterative computer methods and N.O.E. measurements. The results indicate that the major solution conformation of the pyranoid ring of the derivatives in the $\text{D}$-gluco series $\text{1}$, $\text{5}$ and $\text{9}$ may be described as flattened ⁴C₁ and that of $\text{7}$ and $\text{10}$ as ²$\text{S}$₅. The major solution conformation of the pyranoid ring in all compounds in the $\text{D}$-galacto series ($\text{2}$,$\text{4}$,$\text{6}$,$\text{8}$) may be described as flattened ⁴$\text{C}$₁.     

Large scale synthesis and absolute configuration of (-)-3-ppp,a selective dopamine autoreceptor agonist

A large scale synthesis for (-)-3-PPP has been developed. The racemic methoxy compound $\text{1}$ was prepared in a three step procedure in 63% yield. This was resolved as a diastereomeric salt by crystallization of the (-)-di-p-toluoyltartrate. Two crystallizations gave the pure (-)-enantiomer $\text{2}$ in 50% of the theoretical yield and with an enantiomeric excess of >95%. Demethylation using aqueous HBr gave (-)-3-PPP, ($\text{3}$). Compound $\text{2}$ was also prepared in a stereoselective synthesis from $\text{S}$-(-)- N-propyl-2- chloromethylpyrrolidine $\text{4}$. By X-ray crystallography it was shown that (-)-3-PPP has the $\text{S}$-configuration at the chiral carbon.     

Synthesis of 4-substituted cis,cis-1,6-cyclodecadienes via cycloalkylation

Cycloalkylation of dimethyl malonate and tosylmethylisocyanide with $\text{cis}$,$\text{cis}$-1,9-dibromonona-2,7-diene has demonstrated the feasibility of direct cyclization as a route to functionalized $\text{cis}$,$\text{cis}$-1,6-cyclodecadienes.     

Conformation,in solution,of c-4-t-butyl-1-phenyl-r-1-(N-piperidyl)cyclohexane hydrochloride. The conformational energy of t-butyl

Although the hydrochloride of $\text{c}$-4-$\text{t}$-butyl-1-phenyl-$\text{c}$-1-(N-piperidyl)cyclohexane crystallizes in the conformation with axial $\text{t}$-butyl, it exists as an almost equimolar mixture of the two chair conformers in CD₂ Cl₂ solution. The position of equilibrium allows one to calculate ΔG°_{$\text{t}$-Bu} as ?4.9 kcal/mol.     

Stereochemical studies — 79 synthesis and kinetic study on the retrodiene decomposition of norbornene-condensed 1,3-oxazin-4-ones

The $\text{cis}$-$\text{cxo}$- amino acid $\text{c}$ with norbornene skeleton was converted into 2-aryvl-$\text{cis}$-$\text{cxo}$-1,3-oxazin-4-ones $\text{5a}$-$\text{d}$. These compounds, similarly to the $\text{diendo}$ isomers $\text{1a}$-$\text{d}$ studied by us earlier, undergo retrodiene decomposition under mild conditions to give 2-aryl-6$\text{2}$-l,3-oxazin-6-ones ($\text{2}$$\text{a}$-$\text{d}$) in 50-60% yield. The ratio of the decomposition rate constants of the tricyclic $\text{diendo}$ and $\text{diexo}$-1,3-oxazin-4-ones, measured in toluene solution, is about 2.     

The resolution of racemic 2-alkyl-1-aminocyclopropane-1-carboxylic acids

Practical procedures for the resolution of racemic modification of (1$\text{R}$, 2$\text{S}$)-and (1$\text{S}$, 2$\text{R}$)-1-amino-2-ethylcyclopropane-1-carboxylic acid $\text{1a}$,$\text{b}$,(1$\text{R}$, 2$\text{S}$)- and (1$\text{S}$, 2$\text{R}$)-1-amino-2-methylcyclopropane-1-carboxylic acid $\text{2a}$,$\text{b}$, and (1$\text{R}$, 2$\text{R}$)- and (1$\text{S}$, 2$\text{S}$)-1-amino-2-methylcyclopropane-1-carboxylic acid $\text{3a}$,$\text{b}$ are described; the structures as $\text{1a}$,$\text{2a}$, and $\text{3a}$ were confirmed by X-ray-crystallographic methods.     

Chiral leaving group: asymmetric synthesis of limonene and bisabolene

The biogenetic-type asymmetric synthesis of limonene and bisabolenes is described. As model studies for the present asymmetric synthesis, the cyclization of catechol, biphenol and binaphthol mononeryl ethers $\text{1}$, $\text{4}$, and $\text{5}$, with organoaluminum reagents are executed to furnish limonene as a major product. Since the reaction of $\text{1}$, $\text{4}$, and $\text{5}$ has proved to proceed much faster than that of neryl phenyl ether under the similar conditions, the rate acceleration is attributed to the novel metal-anchimeric assistance of the aluminum reagents bound with the neighboring hydroxyl group for effecting the generation of the allyl cation. This anchimeric effect is utilized for the enantioselective cyclization of (R)-(+)-1,1'-bi-2-naphthol mononeryl ether ($\text{8}$) upon treatment with modified aluminum reagent $\text{9}$ to produce limonene with high optical purity (77% ee). In a similar fashion, (R)-(+)-binaphthol ($\text{Z}$,$\text{Z}$)-mono-farnesyl ether $\text{16a}$ undergoes the enantioselective cyclization to give β-bisabolene in 76% ee.     

Completely stereoselective synthesis of all four stereoisomeric 1-carbamoyloxy-1,3-alkadienes via anti-diastereoselective homoaldol reaction from aldehydes and a single carbon-three-unit

Lithiation of both ($\text{Z}$)- and ($\text{E}$)-3-trimethylsilyl-2-propenyl $\text{N}$,$\text{N}$-diisopropyl carbamate 2 affords the (2$\text{E}$) -lithium compound 3. Aluminium- or titanium-mediated addition to aldehydes, 4 gives (1$\text{E}$)-(3$\text{R}$*4$\text{S}$*)-enol carbamates 7. A stereospecific Peterson elimination (borontriflouride- or base-mediated) introduces the second double bond either with (3$\text{E}$)- or with (3$\text{Z}$)-configuration. So just by reagent selection for each of the two steps, (1$\text{E}$,3$\text{E}$)-, (1$\text{E}$,3$\text{Z}$)-, (1$\text{Z}$,3$\text{E}$)-, or (1$\text{Z}$,3$\text{Z}$)- dienes 8 - 11, respectively, are prepared with stereoselectivities up to > 99.7%     

Stereochemical studies 87saturated heterdcycles 82: Synthesis and steric structure of steredisomeric n-substituted tetrahydro-1,3-oxazines fused with norbornane or norbornene

$\text{diendo}$- and $\text{diexo}$-2-Methylamino and 2-benzylamino-3-hydroxymethylbicyclo [2.2.1]heptanes and the corresponding bicycio [2.2.1] heptenes ($\text{5a}$ -$\text{d}$, $\text{7a}$ -$\text{d}$) were synthesized from β-amino acid esters containing the norbornane or norbornene skeleton ($\text{3a}$-$\text{d}$). The aminoalcohols were converted to 5,8- methano -3,1-benzoxazines by reaction with formaldehyde. As established by ¹H and ¹³C NMR spectroscopy, the predominant conformation is $\text{endo - boat}$ ($\text{B}$) for the $\text{diexo}$, and $\text{exo - boat}$ ($\text{E}$) for the $\text{diendo}$ derivatives.     

The wittig reaction of non-stabilized phosphorus ylides and aromatic aldehydes. Studies on erythro and threo β-hydroxyphosphonium salts and the promotion of stereochemical drift by synergism between diastereomers

In deprotonation studies with isomerically pure $\text{erythro}$-3 and $\text{threo}$-3, “retro-Wittig” reaction was only detected for $\text{erythro}$-3. Mixtures of $\text{erythro}$-3 and $\text{threo}$-3, under lithium salt-free conditions, undergo stereochemical drift because of synergism between diastereomeric oxaphosphetanes $\text{cis}$-2 and $\text{trans}$-2 during their decomposition to alkenes.     

Nucleophilic reactions of fluoroolefins. I. Reactions of 1-(2-tetrahydrofuryl)-pentafluoropropene with alkoxide ions

Unlike unsubstituted perfluoropropene [1,2] 1-(2-tetrahydrofuryl)-pentafluoropropene $\text{1}$ reacts with sodium alkoxides in parent alcohol solutions to give 1-alkoxy-1-(2-tetrahydrofuryl)-tetrafluoropropenes $\text{2}$ as major products and 1-alkoxy-2H-1-(2-tetrahydrofuryl)-pentafluoropropanes $\text{3}$ as very minor products. The yield of adducts $\text{3}$ is, to some extent, increased by the reduced basicity of the alkoxide ion. Results are discussed in terms of the supposed properties of the carbanionic intermediates involved.N.m.r., m.s., and i.r. data for, and some chemical properties of compounds $\text{2}$, viz., further reactions with sodium alkoxides and hydrolysis are described.     

Preparation of some highly halogenated derivative of furan

Direct chlorination of 2-(2H-hexafluoropropyl)-tetra- hydrofuran $\text{1}$ gave high yield of 2-(2-chlorohexafluoropropyl)- pentachloro-2,5-dihydrofuran $\text{2}$. Bromination of $\text{1}$ gave very complex mixture of products, from which three compounds, $\text{viz}$. 2-bromo-5-(2H-hexafluoropropyl)-furan $\text{3}$, 3-bromo-5-(2H-hexafluoropropyl)-furan $\text{4}$, and 2,4-dibromo-5-(2H-hexafluoropropyl)furan $\text{5}$ were isolated. Exchange fluorination of $\text{2}$ with dry KF at 240 – 300° led to a stepwise substitution of fluorines for chlorines to give mixtures of chloro-fluoro-2-(2-chlorohexafluoropropyl)-dihydrofurans $\text{7}$,$\text{8}$,$\text{9}$ and $\text{10}$, together with small amounts of 2-(2-chlorohexafluoropropyl)-3,4,5-trichlorofuran $\text{6}$.Exchange fluorination of 3,4-dihalo-2,2,5,5-tetrafluoro- 2,5-dihydrofurans $\text{11a}$ and $\text{11b}$ led to a substitution of fluorine for one vinylic halogen to give 3-halo-2,2,4,5,5-pentafluoro-2,5-dihydrofurans $\text{12a}$ and $\text{12b}$ in good yields.Compounds $\text{2}$ – $\text{12}$ were characterised by n.m.r., m.s., and i.r. spectroscopy and elemental analysis.     

Fluorine-containing seven-membered benzoheterocycles derived from hexafluoropropene oligomers

4-Fluoro-2-($\text{F}$-ethyl)-3-($\text{F}$-methyl)-1, 5-benzoxazepine was prepared by reaction of $\text{F}$-2-methyl-2-pentene with 2-aminophenol in the presence of triethylamine in diethyl ether. The reaction of $\text{F}$-2,4-dimethyl-3-heptene with 2-aminophenol in dimethylformamide gave 7-($\text{F}$-1-methylethyl)-8- ($\text{F}$-ethyl)-9,14-benzoxazepino[4,3-b]1,6-benzoxazepine. Several ortho-bifunctional benzenes reacted similarly with $\text{F}$-2-methyl-2-pentene and $\text{F}$-2,4-dimethyl-3-heptene to give the corresponding seven-membered benzoheterocycles.     

Stereochemical studies—971a. Saturated heterocycles—991b : An unusual ring-opening reaction of 2-methylthio-3,1-perhydro-benzoxazines. A comparative study of the 3,1 and 1,3-isomers

In the reactions of 2-thioxo-$\text{cis}$- and $\text{trans}$-3,1-perhydrobenzoxazines ($\text{3}$, $\text{4}$) with methyl iodide the hydrogen iodide formed in the S-methylation process brings about ring-opening and gives iodomethylthiolcarbamates ($\text{7}$, $\text{8}$). Under similar conditions, the thioether salts ($\text{15}$, $\text{16}$) of the structurally isomeric $\text{cis}$- and $\text{trans}$-2-thioxo-1,3-perhydrobenzoxazines, corresponding to the unstable intermediates in the former reactions, are stable. Under more vigorous conditions, the $\text{cis}$ isomer thioether salt $\text{15}$ is transformed into the corresponding $\text{cis}$-and $\text{trans}$-l,3-perhydrobenzoxazin-2-ones ($\text{17}$, $\text{18}$) by ring-opening and subsequent ring-closure, whereas the $\text{trans}$ isomer $\text{16}$ gives only $\text{trans}$-1,3-perhydrobenzoxazin-2-one ($\text{18}$).     

Synthesis of the cyanohydrin of methyl perfluoroheptyl ketone and reaction of the ketone with hydrogen cyanide

The cyanohydrin of methyl perfluoroheptyl ketone $\text{2}$ was able to be synthesized by a two-step process, $\text{i.e.}$, an addition of sodium bisulfite and subsequent treatment with sodium cyanide. When equimolar amounts of ketone 2 and sodium cyanide were reacted in water or dipolar aprotic solvent such as dimethyl-formamide, acetonitrile, 1,2-dimethoxyethane and tetrahydrofuran, cyclic addition products composed of two molecules of ketone $\text{2}$ and one molecule of hydrogen cyanide were exclusively formed as 2,5-dimethyl-2,5-bis(perfluoroheptyl)-4-oxazolidone $\text{6}$ and 2,5-dimethyl-2,5-bis(perfluoroheptyl)-1,3-dioxolane-4-one $\text{7}$ instead of the cyanohydrin of ketone $\text{2}$. It is conceivable that a solubility characteristic of a compound carrying a long perfluoroalkyl group is responsible for the exclusive formation of cyclic compounds $\text{6}$ and $\text{7}$     

Stereochemical studies 83 saturated heterocycles 76 : Preparation and conformational study of partially saturated 3,1-benzoxazines, 3,1-benzoxazin-2-ones and 3,1-benzoxazine-2-thiones

The $\text{cis}$- and $\text{trans}$-2-amino-4-cyclohexene-1-carboxylic acids $\text{1}$ and $\text{3}$ react with imidates to give the condensed-skeleton, bicyclic $\text{cis}$- and $\text{trans}$-pyrimidin-4-ones $\text{8}$ and $\text{9}$. The amino acids $\text{1}$ and $\text{3}$ were reduced to the $\text{cis}$-and $\text{trans}$-1, 3-aminoalcohoIs $\text{6}$ and $\text{7}$, which were cyclized by means of imidates to the bicyclic tetrahydro-4$\text{H}$-3,1-benzoxazines $\text{10}$ and $\text{11}$, or were converted, $\text{via}$ the corresponding carbamates $\text{14}$ and $\text{15}$ into the tetrahydro-4$\text{H}$-3,1-benzoxazin-2(1$\text{H}$)-ones $\text{16}$ and $\text{17}$. The 2-thioxo analogues $\text{18}$ and $\text{19}$ were prepared by cyclization of the dithiocarbamates obtained from the aminoalcohols $\text{6}$ and $\text{7}$ by treatment with carbon disulphide. The $\text{trans}$-aminoalcohol $\text{7}$ and its saturated analogue reacted with $\text{p}$-chlorobenzaldehyde to furnish the hexahydro $\text{13}$ and octahydro-4$\text{H}$-3,1-benzoxazine $\text{13a}$, respectively. ¹H and ¹³C NMR studies showed that, similarly to the earlier-investigated analogues containing oxygen or unsubstituted nitrogen at position 1, the synthesized $\text{cis}$ isomrs $\text{8}$, $\text{10}$, $\text{16}$ and $\text{18}$ occurred as the preferred conformer in the heterocyclic twist inverse form of $\text{N}$-inside type ($\text{quasiaxial}$ C₆-N bond) (B). In the $\text{trans}$ isomers containing a saturated C-2 atom ($\text{13}$ and $\text{13a}$), H-2 and H-6 are in $\text{cis}$ relative positions.     

Fluorinated chromenes 1: 2,2,2-trifluoroethoxy precocene analogs and their corresponding 3,4-epoxides

Preparation of potential insect antijuvenile hormone agents 2,2-dimethyl-7-(2,2,2-trifluoroethoxy)-2H-chromene ($\text{3a}$), 6-methoxy-2,2-dimethyl-7-(2,2,2-trifluoroethoxy)-2$\text{H}$-chromene ($\text{3b}$) and 7-methoxy-2,2-dimethyl-6--(2,2,2-trifluoroethoxy)-2$\text{H}$-chromene ($\text{3c}$) and the corresponding 3,4-epoxides $\text{5a}$ and $\text{5b}$ is reported.     

Cycloaddition reactions of 2,3-didehydrothiophene generated by flow vacuum thermolysis of thiophene-2,3-dicarboxylic anhydride

Flow vacuum thermolysis (FVT) of thiophene-2,3-dicarboxylic anhydride ($\text{2}$) in the presence of 2,3-dimethylbutadiene ($\text{6}$) gives, in addition to 5,6-dimethylthianaphthene ($\text{9}$). small quantities of a dihydrodimethylthianaphthene ($\text{12}$) and another dimethylthianaphthene ($\text{13}$) which is probably also formed by dehydrogenation of $\text{12}$ with chloranil. The partial structures of these minor products are consistent with their being formed by a [2+2]-cycloaddition between $\text{6}$ and an intermediate aryne, 2,3-didehydrothiophene ($\text{1}$), followed by a rearrangement of the resulting adduct $\text{11}$ and dehydrogenation. FVT of $\text{2}$ in the presence of 2,5- ($\text{17b}$) or 3,4-dimethylthiophene ($\text{17c}$) also gave a mixture of the dimethylthianaphthenes ($\text{18}$$\text{22}$, $\text{23}$) which can be rationalized as arising by a [4+2]- and two [2+2]-cycloadditions of the aryne $\text{1}$ to the thiophenes $\text{17}$ with subsequent desulfurization. The lack of equilibration of the products $\text{18}$, $\text{22}$ and $\text{23}$, was demonstrated and their origin as a function of the structure and reactivity of the aryne $\text{1}$ discussed.