(+)- and (-)-1-0, 4-0-bis(p-chlorobenzyl)threitol as novel resolving agents for optically active anthracyclinone synthesis: an efficient synthesis of optically pure 4-demethoxydaunomycinone

(±)-7-Deoxy-4-demethoxydaunomycinone(±)-$\text{3}$) was cleanly resolved by forming a mixture of the diastereomeric acetals ((?)-$\text{9}$ and (+)-$\text{10}$ or (+)-$\text{9}$ and (?)-$\text{10}$ with the title $\text{vicinal}$-diol((+)- or (?)-$\text{5}$) to give optically pure (R)(?)-$\text{3}$. The method for racemizing the undesired enantiomer((S)(+)-$\text{3}$) was also explored. Optically pure (+)-4-demethoxydauno-mycinone ((+)-$\text{2b}$) was elaborated from (R)(-)-$\text{3}$ according to the reported reaction scheme.     

Regioselective intramolecular asymmetric cyclization of symmetrical open chain triketone

The title reactions performed with (S)-α-amino acids or their derivatives as chiral sources were found to regioselectively give enantiomeric pairs of optically active 4-acetyl-3, 4-dimethyl-2-cyclohexenone (R)(+)- and (S)(?)-$\text{4}$), 16–25% e.e., and those of optically active 6-acetyl-3,6-dimethyl-2-cyclohexenone((R)(+)- and (S)(?)-$\text{5}$, 54–59% e.e., from the open chain triketone($\text{3}$).     

Synthesis of enantiomerically enriched atrolactic acid and other α-hydroxy acids

The α-anions of 2-substituted 1,3-dioxolan-4-ones derived from chiral mandelic and lactic acid ($\text{2a}$, $\text{2b}$; $\text{3a}$; $\text{10a}$, $\text{10b}$) were alkylated with high stereoselectivity. The products formed were hydrolysed to α-hydroxy acids with 65–85% e.e. ((S)(+)-$\text{5}$,$\text{7}$,$\text{9}$, (R)(–)-$\text{13}$).     

Formal total synthesis of β-pipitzol

(±)-$\text{O}$-methylperezone ($\text{1b}$) was obtained by selective oxidative demethylation of (±)-leucoperezone trimethyl ether ($\text{4a}$). Compound ($\text{4a}$) was prepared by condensation of 2,3,5-trimethoxytoluene ($\text{5e}$) with 6-methyl-5-hepten-2-one, followed by reductive removal of the tertiary alcohol. The aromatic precursor $\text{5e}$ was prepared in four steps from 2,3-dimethoxytoluene ($\text{5a}$) and, alternatively, in three steps from 5-bromoveratraldehyde ($\text{6a}$). Racemic $\text{1b}$ and $\text{4a}$ were directly compared with the optically active molecules prepared from natural R(-)-perezone ($\text{1a}$).     

Novel resolution of the anthracyclinone intermediate by the use of (2r, 3r)-(+)- and (2s, 3s)-(-).1,4-bis(4-chlorobenzyloxy)butane-2,3-diol: a simple and efficient synthesis of optically pure 4-demethoxydaunomycinone and 4-demethoxyadriamycinone

(±)-7-Deoxy-4-demethoxydaunomycinone((±)-3) was found to be cleanly resolved by forming a mixture of the diastereomereic acetals((-)-9and(+)-10 or(+)-9 and(-)-10)with the title vicinal-diol(+)-or ( )-5), affording optically pure (R)-( )-3. The resolving agents (( + )- and ( )-5) were readily synthesized from unnatural(2S,3S)-(-)-tartaric acid((-)-6)or D-(-)-mannitol and natural (2R,3R)-(+)-tartaric acid((+)6), respectively. The undesired enantiomer ((S)-(+ )-3) obtained by the optical resolution could be racemized by heating with trifluoromethanesulfonic acid in aq acetic acid. Optically pure (R)-3 was elaborated to optically pure (+)-4-demethoxydaunomycinone ((+)-2b) and (+)-demethoxyadriamycinone ((+)-2a) by featuring highly stereoselective ( ? 20:1) introduction of the OH group into the C₇-position as a key step.     

Reactions of β-substituted amines-IV: Kinetics and stereochemistry of the thermal to (r) 3-chloro-1-ethylpiperidine,and the stereo-chemical course of their reactions with nucleophiles

The rate of the thermal rearrangement of (S) 2 chloromethyl-1-ethylpyrrolidine [(S)-1a] to (R)-3-chloro-1-ethylpiperidine [(R) 2a] has been examined at three temperatures in benzene by PMR and polarimetry. The rearrangement was shown to be completely stereospecific and to obey a simple first order rate law. The calculated E_a ΔH3 and ΔS3 were 22 ± 2 $\text{kcal}\text{mole}$ (25°), 21 ± 2.5 $\text{kcal}\text{mole}$ (25°) and - 10 ± 2 e.u. (0°K) respectively. The effect of solvents having differing dielectric constants was also studied. A transition state 9'a and an ion pair intermediate 3a are suggested for the rearrangement. The stereochemical course of the reactions of (S)-1a, (R)-2a and (S)-2a with hydroxide and methoxide ions have been shown to be 100% stereospecific with an uncertainty of about 1%. The absolute configurations of all optically active reactants and products [(S)- and (R)-4a, (S)-4b (R)- and (S)-5a, (R)-5b, (S,S')-6a, (S,R')-7a and (R,R')-8a] were established by chemical correlations with known compounds or by ORD and chemical inference. The ring opening of both the primary and secondary aziridinium ion positions of 1-azonia-1-ethylbicyclo [3.1.0]hexane [(S)-3a] by nucleophiles proceeds entirely by S_N2 processes. The conversion of (R)-1-ethyl-3-hydroxypiperidine [(R)-5a] to (S)-2a. HCl with thionyl chloride in chloroform proceeds by inversion with 4.8% racemization, whereas the thermal rearrangement of (S)-1a to (R)-2a occurs with complete retention of absolute configuration.     

Synthesis of the dioxabicyclononane unit of tirandamycin

A seven-step synthesis of (±)-$\text{3b}$ an advanced, common intermediate for construction of the dioxabicyclononane units of both tirandamycin and streptolydigin from $\text{14}$ is described (Scheme 1). Conversion of $\text{3b}$ to the fully developed fragment of tirandamycin is also reported.     

Studies directed towards the asymmetric total synthesis of antileukemic lignan lactones. Synthesis of optically pure key intermediate and its utility

By the self-immolative asymmetric synthesis, optically pure key intermediate β-piperonyl-γ-lactone (R)-(+)-$\text{6}$ was found to be prepared in reasonable yield from the easily available chiral γ-lactone synthon ($\text{1}$) which had been also reported to give an antipode (S)-(-)-$\text{6}$. The optically pure (R)-(+)-$\text{6}$ was shown to be converted successfully into several optically pure natural lignan lactones.     

Synthesis of 2-isopropylfuro(2,3-b)quinolines-a new synthesis of (±)-lunacrine, (±)-lunasine and (±)-demethoxylunacrine

A new and convenient synthesis of 2-isopropylfuro-(2,3-b)quinolines ($\text{4}$) from 3-(3-methylbut-1-enyl)-2-quinolones ($\text{2}$) is described. A neat synthesis of the alkaloids (±)-lunacrine ($\text{1a}$), (±)-lunasine ($\text{12a}$) and (±)-demethoxylunacrine ($\text{1b}$) is also reported.     

Structure and synthesis of physoperuvine: x-ray crystal and molecular structures of the n-benzoyl derivatives of (±)-3- and (+)-4-methylaminocycloheptanone

Single-crystal X-ray analyses have defined the structures and solid-state conformations of (±)-N-benzoyl-3-methylaminocycloheptanone [(±)-$\text{3}$]and (+)-N-benzoyl-4-methylaminocycloheptanone [(±)$\text{4}$]. Resolution of (±)-[4- methylaminocycloheptanone α 1-hydroxytropane]to yield the (+)-enantiomer. Identical in all respects with the free base from natural (+)-physoperuvine, was achieved via the di-p-toluoyl-(+)-tartrate salt.     

Amino substituted 1-oxa-3-azabutatrienium salts: preparation, structure and reaction with carbonyl compounds

N,N-Dimethylformamide ($\text{4a}$) and N,N-dimethylpivalamide ($\text{4b}$) react with carbonyl chloride isocyanate ($\text{5}$) in the presence of antimony pentachloride to afford the amino substituted 1-oxa-3-azabutatrienium hexachloroantimonates $\text{6a}$,$\text{b}$. An X-ray diffraction analysis of $\text{6a}$ confirms the proposed structure. The heterocumulenes $\text{6a}$,$\text{b}$ react with aldehydes, ketones and tertiary carboxamides to give the amino substituted 2-azaallenium salts $\text{13a}$-$\text{O}$ in high yields.     

Chiral aminoacid containing macrocycles

Optically active macrocycles (R, R)-$\text{8}$-$\text{10}$ and diastereomeric mixtures of (±)-$\text{8}$-$\text{10}$ and meso-(R, S)-$\text{8}$-$\text{10}$ were prepared containing two (R)- or (S)-α-phenylglycine units as sources of chirality.     

Total syntheses of (±)-isoagatholactone and (±)-12α-hydroxyspongia-13(16),14-dien

(±)-Isoagatholactone $\text{1}$ and (±)-12α-hydroxyspongia-13(16),14-dien $\text{2b}$, a fundamental skeleton of spongiadiol $\text{2a}$ and its congeners, have been synthesized from (±)-labda-8(20),13-dien-15-oic acid $\text{3}$.     

2-cyano Δ3 piperidines vi1 : a general method for the stereoselective synthesis of cis and trans 2,6-dialkylpiperidine alkaloids

The cis 2,6-dialkylpiperidine alkaloid (±) dihydro-pinidine $\text{7b}$ and the trans alkaloid (±) solenopsin A $\text{5a}$ were synthesized from a common α-aminonitrile synthon $\text{1}$. The key step in this synthesis was the stereoselective reductive decyanation of the 1-benzyl-2cyano-2′, 6-dialkylpiperidines $\text{3a}$ and $\text{3b}$.     

Biomimetic synthesis of (±) panacene

(±) Panacene $\text{1a}$ and (±) 1-epibromopanacene $\text{1b}$ have been synthesized by a biomimetic brominative cyclization of hydroxyenyne $\text{4}$.     

A practical process for large-scale synthesis of (S)-5-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-HETE)

($\text{S}$)-5-Hydroxy-6-$\text{trans}$-8,11,14-$\text{cis}$-eicosatetraenoic acid (5-HETE) (1) and its enantiomer are readily available by a chemical synthesis from arachidonic acid which includes a chromatographic separation of diastereomeric urethanes (3) made from (±)-5-HETE methyl ester and the isocyanate 4 derived from dehydroabietylamine.     

A novel synthesis of (±)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthol,a key intermediate for the synthesis of anthracyclinones

The title compound((±)-3) was prepared from readily available 5,8-dimethoxy-3,4-dihydro-2-naphthoic acid(4), according to the novel synthetic route visualized in $\text{Scheme I}$.     

Biotin biosynthesis. Incorporation of 5(RS)-3H-Dethiobiotin into biotin

5(RS)-³H-(±)-Dethiobiotin has been synthesized and its incorporation into biotin by $\text{Aspergillus}$$\text{niger}$ has been investigated. The incorporation was found to proceed without tritium loss.     

The absolute configurations of (+)-thalictrifoline and (+)-corydalic acid methyl ester. Total synthesis of (+)-thalictrifoline.

(+)-Thalictrifoline ($\text{3}$) has been synthesized from an optically resolved (+)-8-oxo-13-carboxytetrahydroprotoberberine ($\text{13}$) whose absolute configuration was established by correlation with (+)-$\text{18}$. This determines the absolute configurations of (+)-thalictrifoline ($\text{3}$) as 13R, 14R aria (+)-corydalic acid methyl ester ($\text{9}$) as 3R, 4R.     

Photocyclization of n-[ω-(cycloalken-1-yl)alkyl]-and n-[ω-(inden-3-yl)alkyl]phthalimides : Synthesis of spiro-nitrogen multicyclic systems

Photolysis of the N-[ω-(cycloalken-1-yl)alkyl]phthalimides 6b-$\text{e}$ in each case gave a pair of stereoisomers of spiro-nitrogen multicyclic systems (9b-$\text{e}$) in moderate yields, whose stereochemistry was determined by means of chemical and spectroscopic analyses. Similarly, in N-[ω-(inden-3-yl)alkyl]-phthalimides (8), spiro-nitrogen macrocycles up to 13-membered 13a-$\text{c}$ were obtained in good yields