Asymmetric total synthesis of dibenzocyclooctadiene lignan natural products

[structure: see text] Full details of the asymmetric total syntheses of the dibenzocyclooctadiene lignans interiotherin A, angeloylgomisin R, gomisin O, and gomisin E (epigomisin O) are presented. The syntheses were based on a unified synthetic strategy involving a novel crotylation using the Leighton auxiliary that occurred with excellent asymmetric induction (>98:2 enantiomeric ratio), a diastereoselective hydroboration/Suzuki-Miyaura coupling reaction sequence, and an atropdiastereoselective biarylcuprate coupling, both of which occurred with total (>20:1) stereocontrol. The syntheses were achieved in six to eight steps from simple aromatic precursors.     

New dibenzocyclooctadiene lignans from the Kadsura ananosma

Fourteen new dibenzocyclooctadiene lignans, ananonins A-N (1-14), together with five known compounds, were isolated from the seeds of Kadsura ananosma. The structures and absolute configurations of 1-14 were established using a combination of MS, NMR, and CD techniques. The biological activity of these compounds was evaluated, and ananonin M (13) showed moderate neuroprotective effects in an in vitro assay.     

Asymmetric synthesis of homochiral dibenzylbutyrolactone lignans by conjugate addition to a chiral butenolide

Addition of sulphur stabilised carbanions to a chiral non-racemic butenolide followed by reaction with an aromatic aldehyde affords a short synthesis of homochiral dibenzylbutyrolactone derivatives. Desulphurisation of the first formed adducts proceeds in almost quantitative yield to afford the parent lignan.     

Carbonium cyclization—studies on lignans containing the dibenzocyclooctadiene system,II

Studies of schisandrol B under Ritter reaction conditions showed similar results to that of schisandrin. However the carbonium cyclization product (4a) of schisandrol B undergoes oxidative ring opening when exposed to the air. Cyclization of schisantherin A (2) also occurs by treatment with thionyl chloride in pyridine. Here the presence of the extra benzoyloxy group somehow confers stability to the diosphenol system and 8 has to be stirred in solution under oxygen for extended periods to effect ring opening.     

Carbonium cyclization—studies on lignans containing the dibenzocyclooctadiene system,I

The reaction of schisandrin (1) under Ritter reaction conditions (cone, sulfuric acid / acetonitrile) was studied. Besides trace amounts of normal products (7α- and 7β-acetamido derivatives 2a and 2b), the main product was a carbonium cyclization compound (3a).     

A new triterpene and dibenzocyclooctadiene lignans from Schisandra propinqua (WALL.) BAILL

A new triterpene and two new natural dibenzocyclooctadiene lignans were isolated from the stems of Schisandra propinqua. In addition, three known lignans, octadecanoic acid, 2,3-dihydroxypropyl ester and beta-sitosterol were isolated. The structures of the new triterpene and new natural products were elucidated base on spectral analysis, including 1D and 2D NMR experiments. The isolates were tested for their cytotoxic effects against several tumor cell lines by MTT assay.     

Complete assignments of 1H and 13C NMR data for new dibenzocyclooctadiene lignans from Kadsura oblongifolia

Two new dibenzocyclooctadiene lignans, named kadoblongifolins A (1) and B (2), and one new natural product dibenzocyclooctadiene lignan, named kadoblongifolin C (3), were isolated from the stems of Kadsura oblongifolia (K. oblongifolia), together with five known ones, schizanrin F (4), propinquanin C (5), schisantherin G (6), heteroclitin Q (7), kadsurarin (8). The structures of these new lignans were elucidated by a combination of high‐resolution electron ionization mass spectrometry (HR‐EI‐MS), ¹H NMR, ¹³C NMR, HMQC, HMBC, and NOESY spectra. Copyright © 2009 John Wiley & Sons, Ltd.     

Asymmetric synthesis of (S,R)- and (R,R)-methiin stereoisomers

Abstract

An asymmetric synthesis of (+)- and (–)-methiine (S-methyl-(R)-cysteine sulfoxide) diastereomers has been developed. These natural sulfur compounds were isolated from a variety of Brassica vegetables. As the starting compound, (R)-cysteine was used, which was methylated to form (R)-S-methylcysteine. Then the oxidation of S-methylcysteine with tert-butyl hydroperoxide catalyzed by the chiral tetra(isopropylate)titanium/(S)- or (R)-Binol complex led to the formation of (1?R,2S)-(+)- or (1?R,2R)-(–)-methiin stereomers.     

Asymmetric synthesis of (2S,3R)-capreomycidine and the total synthesis of capreomycin IB

A 27 step total synthesis of the tuberculostatic macrocyclic peptide antibiotic capreomycin IB has been accomplished. The synthesis features the use of an enolate-aldimine condensation between a chiral glycine aluminum enolate and the benzyl imine of 3-tert-butyldimethylsiloxy-propanal as a means of preparing the cyclic guanidine amino acid (2S,3R)-capreomycidine. Additionally, a Hofmann rearrangement was exacted on a late-stage pentapeptide in order to transform an asparagine residue into a diaminopropanoic acid residue.     

Catalyzed cyclizations leading to enrichment of functionality and chirality. A general approach to dibenzocyclooctadiene lignans from alpha,omega-diynes

The [B-Sn]-mediated cyclization of alpha,omega-diynes results in not only an increase in the functionalizable groups (incorporated as highly versatile vinyl-B and vinyl-Sn groups) but also an increase in new serviceable stereochemical elements. The alkylidene functionalities at C7 and C8 offer unprecedented opportunities for the synthesis of highly functionalized dibenzocyclooctadienes. Examples of interiotherins and gomisins are provided.     

Asymmetric synthesis of (2S,3R,4R)-ethoxycarbonylcyclopropyl phosphonoglycine

The synthesis of enantiomerically pure (2S,3R,4R)-ethoxycarbonylcyclopropyl phosphonoglycine is described, the key-step involving 1,4-addition of a chiral enolate to ethyl 4-bromo-crotonate.     

An efficient method for the synthesis of lignans

An efficient approach for the synthesis of several types of lignans (dibenzylbutanediols, dibenzylbutanes, substituted tetrahydrofurans, aryldihydronaphthalenes, arylnaphthalenes, and aryltetralins) was developed. The regioselective oxidative coupling of ethyl ferulate was used as the key step.     

Asymmetric synthesis of (1R,2S,3R)-gamma-methyl-cis-pentacin by a kinetic resolution protocol

The asymmetric synthesis of (1R,2S,3R)-3-methyl-2-amino-cyclopentane carboxylic acid has been achieved via kinetic resolution of racemic tert-butyl 3-methyl-cyclopentene-1-carboxylate with homochiral lithium (S)-N-benzyl-N-alpha-methylbenzylamide.     

Asymmetric synthesis of (4R,5R)-cytoxazone and (4R,5S)-epi-cytoxazone

(4R,5R)-Cytoxazone has been prepared in four steps and in 61% overall yield and >98% ee. Conjugate addition of lithium (R)-N-benzyl-N-[small alpha]-methylbenzylamide to tert-butyl (E)-3-(p-methoxyphenyl)prop-2-enoate and subsequent in situ diastereoselective enolate oxidation with (+)-(camphorsulfonyl)oxaziridine gave tert-butyl (2R,3R,[small alpha]R)-2-hydroxy-3-(p-methoxyphenyl)-3-(N-benzyl-N-[small alpha]-methylbenzylamino)propanoate in >98% de. Subsequent N-benzyl deprotection to the primary [small beta]-amino ester via hydrogenolysis, oxazolidinone formation with C(2)-retention by treatment with diphosgene and chemoselective ester reduction furnishes (4R,5R)-cytoxazone. The synthesis of the C(5)-epimer, (4R,5S)-epi-cytoxazone in 44% overall yield, has also been completed via a protocol involving N-Boc protection of the primary [small beta]-amino ester, utilization of the N-Boc group to facilitate simultaneous C(2)-inversion and oxazolidinone formation, and subsequent reduction.     

Asymmetric synthesis of (R)-(+)-etomoxir via enzymatic resolution

An asymmetric synthesis of (R)-(+)-etomoxir 3, employing enzymatic resolution of ethyl 2-alkyl-2,3-dihydroxypropionate using Amano AK via transacylation is reported.     

An approach to the biomimetic synthesis of aryltetralin lignans

The BF₃ catalysed cyclisation of 3-arylpropyl substituted quinone-methide ketals affords a mild, biomimetic route to aryltetralins. ¹H- and ¹³C-NMR spectra of the products are reported.     

Asymmetric synthesis and conformation

The configuration of the 3-alkyl substituted 1,2,3-triphenyl-1-propanones is proved through use of pseudocontact shifts using Eu(dpm)₃. The conformation of all isomers, regardless of size of R, is similar (trans vicinal protons). The relative stability of the two isomers is also independent of R up to R = t-Bu. The conformation and configuration of the hydride reduction products, the alkyl substituted 1,2,3-triphenyl-1-propanols, are elucidated through use of NMR chemical shifts, coupling constants, pseudocontact shifts, and by IR spectra. The starting materials and reduction products (with one exception) have the same conformation at relevant centers, yet the mode of hydride attack is best explained by means of a different conformation in the transition state, in which the LAH approaches over a proton at either asymmetric center.     

Asymmetric synthesis of (R)-4-hexanolide,the pheromone of Trogoderma glabrum

Synthesis of (R)-4-hexanolide, a sexual pheromone of Trogoderma glabrum, has been achieved with an overall yield of 45.4% in high enantiomeric purity using a chiral auxiliary derived from (S)-camphor.