Über die Synthese der Pilocarpus-Alkaloide Isopilosin und Pilocarpin,sowie die absolute Konfiguration des (+)-Isopilosins

A novel synthesis for rac-pilosinine ( 6 rac) and transformation of (+)-pilosinine ( 6 ) into the pilocarpus alkaloids (+)-isopilosine ( 9 ) and (+)-pilocarpine ( 18 ) are described. By correlation via 5 with 18 the absolute configuration of (+)-isopilosine ( 9 ) is established.     

«Alkaloide» in tierischem und menschlichem Gewebe. 6. Mitteilung [1] [2]. Synthese und absolute Konfiguration chiraler 2, 3, 10, 11 - Tetrahydroxy-8-methyl-berbine [3]

Synthesis and absolute configuration of chiral 2, 3, 10, 11-tetrahydroxy-8-methylberbines [3] . The synthesis and absolute configuration of the four optically active berbines Xa, b and XIa, b are described. These compounds consitute potential ‘alkaloids’ obtained by condensation of either R-(+) or S-(?)-norlaudanosoline (THP, III) with acetaldehyde, a major metabolite of ethanol.     

Sedum alkaloids—VII : Structure and synthesis of (+)-4-hydroxysedamine and (+)-4-hydroxyallosedamine

The structures of (+)-4-hydroxysedamine ¹ and (+)-⁴-H-hydroxyallosedamine ², two new minor alkaloids from Sedum itacre, are reported 1 and 2 were synthesized, and their absolute configuration established, via the optically pure tetrahydro 1,3-oxazines 17 and 18.     

Syntheses of (S)-(+)-trihexyphenidyl hydrochloride and (S)-(+)-procyclidine hydrochloride, two anticholinergics, using (S)-(-)-3-cyclohexyl-3-hydroxy-3-phenylpropanoic acid as chiral synthon

The absolute configuration of the more active (-)-enantiomer of the anticholinergic trihexyphenidyl hydrochloride has been established as (R) by syntheses of (S)-(+)-procyclidine hydrochloride, whose absolute configuration has been established previously, and (S)-(+)-trihexyphenidyl hydrochloride from the same chiral building block, viz. (S)-(-)-cyclohexyl-3-hydroxy-3-phenylpropanoic acid. Both enantiomers of this chiral synthon were prepared by optical resolution of the corresponding racemate, employing (R)- and (S)-1-phenylethylamine, respectively, as resolving agents.     

Chirality and numbering of substituted tropane alkaloids

The strict application of IUPAC rules for the numbering of tropane alkaloids is not always applied by authors and there is hence a lot of confusion in the literature. In most cases, the notation of 3, 6/7-disubstituted derivatives has been chosen arbitrarily, based on NMR and MS data, without taking into account the absolute configuration of these two carbons. This paper discusses the problem and the relevance of CD and NMR to determine molecular configurations. We report on the use of (1)H-NMR anisochrony (Δδ) induced by the Mosher's chiral auxiliary reagents (R)-(-)- and (S)-(+)-α-methoxy-α-trifluoromethyl-phenylacetyl chlorides (MTPA-Cl), to determine the absolute configuration of (3R,6R)-3α-hydroxy-6β-senecioyloxytropane, a disubstituted tropane alkaloid isolated from the aerial parts of Schizanthus grahamii (Solanaceae). These analytical tools should help future works in correctly assigning the configuration of additional 3, 6/7 disubstituted tropane derivatives.     

Biosynthese der Verrucarine und Roridine. Teil 5. Synthese von zwei Diastereoisomerenpaaren des [1,8-14C]-α-Bisabolols und Versuche zu deren Einbau in Verrucarol Verrucarine und Roridine, 32. Mitteilung [1]

The diastereoisomeric (+)-[1,8-¹⁴C]-(1'R,6R, S)-α-bisabolol ( 2a ) and (?)-[1,8-¹⁴C]-(1′S, 6R, S)-α-bisabolol ( 2b ) were synthesized by reaction of the Grignard compound of [1,6-¹⁴C]-5-bromo-2-methyl-2-pentene ( 12 ) with (+)-(R)- and (?)-(S)-4-acetyl-1-methyl-1-cyclohexene, ( 6a ) and ( 6b ) respectively. For the preparation of compound 12, cyclopropyl methyl ketone was treated with [¹⁴C]-methyl magnesium iodide to form the carbinol 11, which was cleaved by HBr. Compounds 6a and 6b were synthesized from (+)-(R)- and (?)-(S)-limonene, ( 4a ) and ( 4b ), via the derivatives 5a , 6a and 5b , 6b respectively. - This synthesis established the absolute configuration at C(1′) of the natural α-bisabolols: (R) for (+)-α-bisabolol and (S) for (?)-α-bisabolol. - Feeding experiments with cultures of Myrothecium roridum and radioactive (+)-(1′R, 6R, S)- and (?)-(1′S, 6R, S)-α-bisabolol ( 2a ) and ( 2b ) gave negative results. These findings indicate that bisabolane derivatives are not intermediates in the biosynthesis of verrucarol (3).     

Use of the oxazole-olefin diels-alder reaction in the total synthesis of the monoterpene alkaloids (-)-plectrodorine and (+)-oxerine

A full account of the total synthesis of two monoterpene alkaloids, (-)-plectrodorine [(-)-1] and (+)-oxerine [(+)-3], is presented. The key steps involved are the formation of the oxazole alcohol 10 from the gamma-butyrolactone 9 and the intramolecular Diels-Alder reaction of the oxazole-olefins 13a, b. Since the sign of specific rotation for the synthetic (+)-3 was different from that reported for natural oxerine, the absolute configuration of this alkaloid is not yet fully understood.     

Synthesis of chiral glycolurils from (<Emphasis Type="Italic">S</Emphasis>)-(+)- and (<Emphasis Type="Italic">R</Emphasis>)-(-)-1-<Emphasis Type="Italic">sec</Emphasis>-butyl-3-methylurea

Chiral dialkyl- and tetraalkylglycolurils have been obtained using chiral (S)-(+)- and (R)-(-)-1-sec-butyl-3-methylurea as starting materials. The diastereomer (S)-(+)-2,6-di-sec-butyl-4,8-dimethyl-2,4,6,8-tetraazabicyclo[3.3.0]-octane-3,7-dione was separated into stereoisomers, for the higher melting of which the absolute configuration was determined as (S,S,S,S) by X-ray structural analysis.     

Konstitution und absolute Konfiguration der Rhoeadin-Alkaloide (+)-Alpinigenin und (+)-cis-Alpinigenin

The constitution and absolute configuration of the rhoeadine alkaloids (+)-alpinigenine and (+)-cis-alpinigenine. The fundamental structure of the hemi-acetal phenylbenzazepine alkaloid (+)-alpinigenine ( 1 ), isolated from Papaver bracteatum LINDL ., was derived essentially from ¹H-NMR.- and mass-spectra of 1 and its derivatives 7, 10 and 14 (cf. Scheme 2). The positioning of the four methoxy groups in the two aromatic rings could be deduced from the ¹H-NMR.-spectra of the N-oxides 14 and 15 in which, as a result of favourable sterical and conformational behaviour, an interaction exists between the N-oxide oxygen atom and one of the two ortho protons in ring C. The B/D-trans-fused 1 undergoes isomerization in 1N HCl to cis-alpinigenine ( 16 ). A stereochemical correlation between bases in the trans-and cis-series was enabled via an Emde degradation of the corresponding methylacetal-methyliodides 21 resp. 19 leading to the enantiomeric isochroman derivatives 22 resp. 23 which are achiral at C (2) (Scheme 4). The configuration at C (14) in the hemi-acetals (eg. 1 and 16 ) and the methyl ethers (eg. 7 and 8 ) is discussed in detail (cf. Scheme 7). (+)-Alpinigenine ( 1 ) has the (1S, 2R, 14R) configuration and (+)-cis-alpinigenine ( 16 ), in chloroform or acetone solution, the (1R, 2R, 14R) configuration.     

Synthese et configuration absolue de terpenes naturels: (+) uroterpenol, (+) et (−) α-bisabolols, (−) α-bisabololone

Stereoisomers of 8,9-epoxy p-menthene-1 have been synthetised and after separation their absolute configurations have been determined. From the (+)-epoxides we obtained isomers of (+)-uroterpenol and (+)-α-bisabolol. From the (?)-epoxides we obtained isomers of (?)-α-bisabololone. Natural (+)-and (?)-α-bisabolols are of configuration (4R, 8S) and (4S, 8R) respectively. Natural (?)-a-bisabololone has the (4S, 8R) configuration.     

Synthesis of Aristotelia-Type Alkaloids. Part XV. Total synthesis of (+)-hobartinol

Synthetic (+)-makomakine ( 6 ) was transformed in six steps into (+)-17R,18R)-17,18-dihydrohobartine-17,18-diol ((+)- 5 ) with an overall yield of 38% (Scheme 2). This compound was shown to be identical with natural hobartinol, a monoterpene indole alkaloid from Aristotelia australasica, originally believed to be the (17S)-epimer 1 . At the same time, the synthesis of (+)- 5 delineates the hitherto unknown absolute configuration of this metabolite.     

Ermittlung der absoluten Konfiguration von Indolinalkaloiden durch Vergleiche der Optischen Rotationsdispersionen ihrer N(a)-Acylderivate

A further application of Optical Rotatory Dispersion (ORD) for indole alkaloids containing an N-acylindoline chromophore has completely substantiated an earlier assignment of the absolute configuration of Aspidosperma alkaloids and has extended the general scope of this method, allowing assignments to the absolute configuration of N(a)-acetyl-aspidospermatidine and limatine.     

Pd-catalyzed enantioselective aerobic oxidation of secondary alcohols: applications to the total synthesis of alkaloids

Enantioselective syntheses of the alkaloids (-)-aurantioclavine, (+)-amurensinine, (-)-lobeline, and (-)- and (+)-sedamine are described. The syntheses demonstrate the effectiveness of the Pd-catalyzed asymmetric oxidation of secondary alcohols in diverse contexts and the ability of this methodology to set the absolute configuration of multiple stereocenters in a single operation. The utility of an aryne C-C insertion reaction in accessing complex polycyclic frameworks is also described.     

Revision of the absolute configuration of the tricyclic sesquiterpene (+)-kelsoene by chemical correlation and enantiospecific total synthesis of its enantiomer

The absolute configuration of the recently identified sesquiterpene (+)-kelsoene was revised by chemical correlation with (R)-(+)-pulegone; the correct structure is (1R,2S,5R,6R,7R,8S)-2,8-dimethyl-6-(1-methylethenyl)tricyclo[5.3.0.0 (2,5)]decane.     

Heterotricyclodecane VIII. (−)-(1S, 3R, 6R, 8R)-2, 7-Dioxaisotwistan und (−)-(1R, 3R, 6R, 8R)-2, 7-Dioxa-twistan; Synthese und Bestimmung der absoluten Konfiguration

A synthesis and the determination of the absolute configuration of (?)-(1S, 3R′ 6R, 8R)-2, 7-dioxa-isotwistane ( 13 ) and (?)-(1R, 3R, 6R, 8R)-2, 7-dioxa-twistane ( 14 ) is described. The results for 14 are compared with those for carboeyclic (+)-twistane ( 2 ) of known chirality.     

Structure and absolute stereochemistry of 19-epi-(+)-echitoveniline : A new indole alkaloid of the leaves of Alstonia venenata r.br.

19-Epi-(+)-echitoveniline, a new indole alkaloid of the leaves ofAlstonia venenata R.Br., has been shown to possess the structure and absolute stereochemistry represented by 5b on the basis of spectral and chemical evidence. A mechanistic rationale for the dependence of the mode of LAH reduction of the δ-lactone 11 on its configuration at C-19 has been offered. The influence of the C-19 configuration on the chemical shift values of the C-16 carbomethoxy protons in the 19-aroyloxy-(+)-and (?)-vincadifformine alkaloids has been discussed.     

Enantioselective total syntheses of nankakurines A and B: confirmation of structure and establishment of absolute configuration

Total syntheses of (+)-nankakurine A (2) and (+)-nankakurine B (3) were accomplished by a sequence that employs an intramolecular dipolar cycloaddition of an azomethine imine intermediate to form the azatricyclic moiety and establish the relative configuration of the spiropiperidine ring. These syntheses, together with the synthesis of the originally purported structure 1 of nankakurine A, rigorously establish the relative and absolute configuration of these structurally unusual Lycopodium alkaloids. The syntheses are sufficiently concise that gram quantities of (+)-nankakurine A (2) and (+)-nankakurine B (3) will be available for further biological studies.     

Cyclobutanones through SNi' ring closure, a mechanistic study

Mechanistic studies on the intramolecular nucleophilic substitution with allylic rearrangement (SNi' reaction) and a new stereoselective access to substituted cyclobutanones are reported. 4,4-Dialkyl-5-oxohex-2E-en-1-yl methanesulfonates 4 were converted to 2,2-dialkyl-3-vinylcyclobutanones 6 by SNi' ring closure. The stereochemical analysis of the reaction was achieved through ring closure of (6S)-6-chloro-3,3-diethylhept-4E-en-2-one (S)-17, defined by the absolute configuration of C(6), leading to (3S)-2,2-diethyl-3-(prop-1E-en-1-yl)cyclobutanone (S)-(E)-18 and (3R)-2,2-diethyl-3-(prop-1Z-en-1-yl)cyclobutanone (R)-(Z)-18, in a ratio of 85:15, with almost complete transfer of chirality (>97%). The absolute configuration of (S)-17 was determined by X-ray diffraction analysis of the camphanoate derivative 16. The absolute configuration of the cyclobutanone products (S)-(E)-18 and (R)-(Z)-18 was determined by Raman optical activity spectroscopy. Comparison of the absolute configuration of (S)-17 and the resulting (E)- and (Z)-cyclobutanones 18 allowed the conclusion that the SNi' reaction proceeds with syn geometry relative to the leaving group.     

Über eine ungewöhnliche Cyclisationsreaktion bei der Umsetzung von (+)-Epoxy-α-dihydrojonon mit Hydrazinhydrat

(+)-Epoxy-α-dihydroionone ( 2 ) is formed completely stereospecifically from (+)-α-ionone ( 1 ). Under the conditions of the Wharton reaction this epoxide gives the expected isomeric allyl alcohols 4 and 5 and, surprisingly, the bicyclic allyl alcohol 3 . The structure and absolute configuration of the reaction products have been established. A common intermediate for the formation of compounds 3, 4 and 5 is probably the vinyl anion C.     

Total synthesis of (+)-benzastatin E via diastereoselective Grignard addition to 2-acylindoline

[reaction: see text] A stereoselective total synthesis of (+)-benzastatin E (1) is described. The synthesis involves a diastereoselective Grignard addition to 2-acylindoline 2, which is derived from commercially available (S)-2-indolinecarboxylic acid (3). The unknown absolute configuration of (+)-1 is determined as (9S,10R).