Total synthesis of (-)-stemospironine

[structure: see text]. A stereocontrolled total synthesis of the polycyclic Stemona alkaloid, (-)-stemospironine (1) has been achieved. Key transformations include the use of a Staudinger reaction leading to the aza-Wittig ring closure of the perhydroazepine system. Formation of the vicinal pyrrolidine butyrolactone is described via the stereoselective intramolecular capture of an intermediate aziridinium salt.     

Ring expansive routes to quinolizidine alkaloids: formal synthesis of (-)-lasubine II

The application of two nitrogen ring expansion reactions to lasubine alkaloid synthesis is reported. The approach involves a conjugate reduction/alkylation sequence carried out on triisopropylsilyl-protected (S)-4-(-)-hydroxycyclopentenone, the formation of the quinolizidone ring system through nitrogen ring expansion, and the addition of an arylmetallic species to the resulting lactam. This work resulted in the preparation of 2-epi-lasubine II and a formal synthesis of lasubine II. [reaction: see text]     

A new approach to (-)-swainsonine by ruthenium-catalyzed ring rearrangement

A new enantioselective synthesis of the idolizidine alkaloid (-)-swainsonine 1 in 40% overall yield starting from the known oxazolidinone 6 is described. Throughout the synthesis, the high efficiency of metal-catalyzed reactions is illustrated. The key step is a new ruthenium-catalyzed metathesis rearrangement reaction. In this ring-closing/ring-opening tandem process, stereocenters are transferred from a ring to the olefinic side chain of the formed heterocycle. The metathesis precursor was obtained by palladium-catalyzed desymmetrization of cyclopentenediol. The synthesis was completed by functionalization of the terminal double bond, cyclization of the second ring, and diastereoselective dihydroxylation.     

Biogenetically inspired approach to the Strychnos alkaloids. Concise syntheses of (+/-)-akuammicine and (+/-)-strychnine

A linear synthesis of the indole alkaloid (+/-)-akuammicine (2) was completed by a novel sequence of reactions requiring only 10 steps from commercially available starting materials. The approach features a tandem vinylogous Mannich addition and an intramolecular hetero Diels-Alder reaction to rapidly assemble the pentacyclic heteroyohimboid derivative 8 from the readily available hydrocarboline 6. Oxidation of the E ring of 8 gave the lactone 9 that was converted into deformylgeissoschizine (11). The subsequent elaboration of 11 into 2 was effected by a biomimetically patterned transformation that involved sequential oxidation and base-induced skeletal reorganization. A variation of these tactics was then applied to the synthesis of the C(18) hydroxylated akuammicine derivative 36. Because 36 had previously been converted into strychnine (1) in four steps, its preparation constitutes a concise, formal synthesis of this complex alkaloid.     

Total synthesis of the Kopsia lapidilecta alkaloid (+/-)-lapidilectine B

The total synthesis of Kopsia lapidilecta alkaloid (+/-)-lapidilectine B is described. Notable elements of this synthesis include the first natural products application of the Smalley azido-enolate cyclization to form the 1,2-dihydro-3H-indol-3-one (indoxyl) core and installation of the pyrrolidine ring by a 2-azaallyllithium [3+2] cycloaddition with the acetylene equivalent phenyl vinyl sulfide. Closure of the eight-membered perhydroazocine ring is accomplished via the intramolecular S(N)2 substitution of a mesylate. This constitutes the first synthesis of a member of the 5,6,12,13-tetrahydro-11a,13a-ethano-3H-pyrrolo[1',2':1,8]azocino[5,4-b]indole class of alkaloids.     

First asymmetric total synthesis of (-)-antofine by using an enantioselective catalytic phase transfer alkylation

[structure: see text] The first asymmetric total synthesis of a potential antitumor phenanthroindolizidine alkaloid, (-)-antofine, is described. An important feature of this synthesis is the creation of a stereogenic center by using enantioselective catalytic phase transfer alkylation, affording an unnatural alpha-amino acid derivative, together with a ring closing metathesis for pyrrolidine ring construction.     

Steroids and sex hormones. Synthesis of 5- and 5- -17-oxo-19-hydroxy-3-aza-3, 19-cyclo-A-homo-androstane

The synthesis of the novel title compounds ( 2 and 3 ) is described. These two isomers differ from structure 1 , ascribed to the salamander alkaloid cycloneosamandione, with respect to ring A/B fusion and to the ketone position.     

A facile asymmetric route to (-)-aphanorphine

8O-methylaphanorphine was synthesized from 4-methoxyphenylacetaldehyde in 36% overall yield and in nine steps, featuring the formation of ring B via a Friedel-Crafts alkylative cyclization with the concomitant stereospecific introduction of the benzylic quaternary carbon center. The current work constitutes an efficient enantioselective formal synthesis of 3-benzazepine marine alkaloid (-)-aphanorphine.     

Total synthesis of indole alkaloid (+/-)-subincanadine F via SmI2)-mediated ring opening and bridge-forming Mannich reaction

The first total synthesis of (+/-)-subincanadine F, a bioactive indole alkaloid structurally featuring a 1-azabicyclo[4.3.1]decane unit, has been realized from 1-(para-methoxybenzyl)tryptamine in six steps. The bridge-containing tetracyclic framework of subincanadine F was efficiently assembled by a SmI2-mediated ring opening followed by an acid-mediated Mannich reaction. In addition, the tetracyclic ketoester 6, a key intermediate potentially useful for synthesizing structurally related indole alkaloids as well, was obtained in one step from alpha,beta-diketoester 5.     

Asymmetric synthesis of (+)-1-epiaustraline and attempted synthesis of australine

A diastereoselective synthesis of the pyrrolizidine alkaloid, (+)-1-epiaustraline has been achieved via a diastereoselective syn-dihydroxylation of a pyrrolo[1,2-c]oxazol-3-one precursor that was readily prepared by a RCM reaction. Attempts to extend this methodology to the synthesis of australine were not successful since the final pyrrolidine ring closure to produce the desired pyrrolizidine of the target molecule was not productive.     

Synthetie approaches to steroidal alkaloids III . An attempted synthesis of ring-e of veratramine

In an effort to devise an alternative synthesis of the hydroxypiperidine ring present in the alkaloid veratramine, a model synthesis starting from cis-6-phenyl-4-heptenoie acid was explored. This acid was converted to the epoxide of cis-6-phcnyl-1-amino-4-hepten which on heating gave 2-( 1-hydroxy-2-phenylpropyl)pyrrolidine as the only produet. As a reference compound, 2-(1-phenylethyl)-3-hydroxypiperidine was synthesized using a variation of an established procedure.     

An approach towards the total synthesis of (+)-epiquinamide and (+)-α-conhydrine from Garner aldehyde

A short and stereoselective route for the synthesis of 1-hydroxyquinolizidine, an advanced synthetic intermediate for the total synthesis of (+)-epiquinamide is presented. The key synthetic steps involve diastereoselective nucleophilic addition on l-serine derived Garner aldehyde and acid mediated (PTSA) ring closing metathesis. The methodology is also elaborated successfully for the total synthesis of (+)-α-conhydrine, an important piperidine alkaloid.     

Reaction of 3-(Arylmethylidene)-1-pyrrolines with Acetone. Synthesis of Norhygrine Derivatives

Russian Journal of Organic Chemistry - An efficient procedure has been developed for the synthesis of analogs of the alkaloid norhygrine by reaction of 3-(arylmethylidene)-1-pyrrolines with...     

Nitrenium ion-mediated alkene bis-cyclofunctionalization: total synthesis of (-)-swainsonine

The total synthesis of (-)-swainsonine from 2,3-O-isopropylidene-D-erythrose in 12 steps and an overall yield of 28% is reported. The pivotal transformation in our route to this indolizidine alkaloid is the formation of the pyrrolidine ring and C-8a/8 stereodiad through the diastereoselective, bis-cyclofunctionalization of an γ,δ-unsaturated O-alkyl hydroxamate. This transformation is believed to proceed via the intramolecular capture of an N-acyl-N-alkoxyaziridinium ion generated by the diastereoselective addition of a singlet acylnitrenium ion to the pendant alkene.     

Photocyclization of 1-(2-halophenyl)-3,4-dihydro-6,7-dimethoxyisoquinolines: a short and new synthesis of triclisine

A short and new synthesis of the non-phenolic azafluoranthene alkaloid triclisine utilizing the photocyclization of 1-(2-halophenyl)-3,4-dihydro-6,7-dimethoxyisoquinolines as a key step has been described.     

A stereodivergent strategy for the preparation of corynantheine and ipecac alkaloids, their epimers, and analogues: efficient total synthesis of (-)-dihydrocorynantheol, (-)-corynantheol, (-)-protoemetinol, (-)-corynantheal, (-)-protoemetine, and related natural and nonnatural compounds

Here we present a general and common catalytic asymmetric strategy for the total and formal synthesis of a broad number of optically active natural products from the corynantheine and ipecac alkaloid families, for example, indolo[2,3-a]- and benzo[a]quinolizidines. Construction of the core alkaloid skeletons with the correct absolute and relative stereochemistry relies on an enantioselective and diastereodivergent one-pot cascade sequence followed by an additional diastereodivergent reaction step. This allows for enantio- and diastereoselective synthesis of three out of four possible epimers of the quinolizidine alkaloids that begin from common and easily accessible starting materials by using a common synthetic route. Focus has been made on excluding protecting groups and limiting isolation and purification of synthetic intermediates. This methodology is applied in the total synthesis of the natural products (-)-dihydrocorynantheol, (-)-hirsutinol, (-)-corynantheol, (-)-protometinol, (-)-dihydrocorynantheal, (-)-corynantheal, (-)-protoemetine, (-)-(15S)-hydroxydihydrocorynantheol, and an array of their nonnatural epimers. The potential of this strategy is also demonstrated in the synthesis of biologically interesting natural product analogues not accessible through synthetic elaboration of alkaloid precursors available from nature, for example, thieno[3,2-a]quinolizidine derivatives. We also report the formal synthesis of (+)-dihydrocorynantheine, (-)-emetine, (-)-cephaeline, (-)-tubulosine, and (-)-deoxytubulosine.     

An aza-Wittig/pi-furan cyclization approach toward the homoerythrina alkaloid (+/-)-selaginoidine

[reaction: see text] A one-pot procedure was developed to efficiently prepare hexahydroindolinones containing a tethered furan ring. Reaction of a furanyl azide with Bu3P delivered the iminophosphorane, which was allowed to react with 1-methyl-(2-oxocyclohexyl)acetic acid to give the desired hexahydroindolinone ring system. Further treatment with trifluoroacetic acid afforded the tetracyclic lactam skeleton found in the alkaloid (+/-)-selaginoidine.     

Facile synthesis of (±)-, (+)-, and (-)-galanthamine

The Amarylidacea alkaloid galanthamine ( 1a ) is an acetylcholinesterase inhibitor that has been evaluated as a potential agent for the treatment of Alzheimer's disease. We report a very efficent synthesis of (±)-galanthamine [(±)- 1a ] from readily available isovanillin and tyramine. We have separated racemic galanthamine into its diastereoisomeric (1S)-camphanate esters and obtained both natural (-)- and unnatural (+)-galanthamine by lithium aluminum hydride removal of the acyl group.     

Alkaloids of Siberia and Altai flora: XVIII. Alkyl 2-acetylamino-5-[2-(pyridin-3-yl)vinyl]benzoates in the synthesis of indolizines containing an anthranilic acid ester moiety

Methyl 2-acetylamino-5-[2-(6-methylpyridin-3-yl)vinyl]benzoate reacted with phenacyl bromide to produce quaternary 1-(2-aryl-2-oxoethyl)-2-methyl-5-(4-acetylamino-3-methoxycarbonyl)pyridinium bromides. 1,3-Dipolar cycloaddition of the latter to methyl propynoate and dimethyl but-2-ynedioate gave the corresponding indolizine derivatives containing an anthranilic acid ester moiety. Reactions of acetylenes with N-phenacylpyridinium salts obtained from a diterpene alkaloid derivative, 2-(pyridin-3-yl)vinyl-substituted lappaconitine afforded analogous compounds in which the indolizine fragment is conjugated to the aromatic ring of the alkaloid. 1,3-Dipolar cycloaddition of 1-(2-aryl-2-oxoethyl)-2-methyl-5-(4-acetylamino-3-methoxycarbonyl) pyridinium bromides with methyl propynoate was regioselective.     

Total syntheses of enantiomerically enriched R-(+)- and S-(-)-deplancheine

Total syntheses of indoloquinolizidine alkaloid (+/-)-, R-(+)-, and S-(-)-deplancheine are described here. The synthesis features an enantioselective intramolecular formal aza-[3 + 3] cycloaddition for the construction of the quinolizidine CD-ring. This application serves to introduce a new synthetic strategy for the synthesis of indoloquinolizidine alkaloids.