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1.
SG Davies JA Lee PM Roberts JP Stonehouse JE Thomson 《The Journal of organic chemistry》2012,77(16):7028-7045
The highly diastereoselective conjugate additions of the novel lithium amide reagents lithium (R)-N-(3-chloropropyl)-N-(α-methylbenzyl)amide and lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)amide to α,β-unsaturated esters were used as the key steps in syntheses of the homalium alkaloids (-)-(S,S)-homaline and (-)-(R,R)-hopromine. The asymmetric synthesis of (-)-(S,S)-homaline was achieved in 8 steps and 18% overall yield, and the asymmetric synthesis of (-)-(R,R)-hopromine was achieved in 9 steps and 23% overall yield, from commercially available starting materials in each case. These syntheses therefore represent by far the most efficient total asymmetric syntheses of these alkaloids reported to date. A sample of the (4'R,4'S)-epimer of hopromine was also produced using this approach, which provided the first unambiguous confirmation of its absolute configuration and therefore that of natural (-)-(R,R)-hopromine. 相似文献
2.
Davies SG Hughes DG Nicholson RL Smith AD Wright AJ 《Organic & biomolecular chemistry》2004,2(10):1549-1553
(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. 相似文献
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Described are the first enantioselective total syntheses of (+)-arborescidine A ((+)-1), (-)-arborescidine B ((-)-2), and (-)-arborescidine C ((-)-3), via routes that proceeded in five steps and 50% overall yield, eight steps and 61% overall yield, and nine steps and 51% overall yield, respectively, from 6-bromotryptamine (7). The syntheses feature the use of the Noyori catalytic asymmetric hydrogen-transfer reaction to introduce chirality in dihydro-beta-carbolines 6 and 8. On the basis of an ample precedent from Noyori's work, the reduction produces dihydro-beta-carbolines, and ultimately the natural products, possessing the R absolute configuration. The synthetic arborescidines displayed optical rotations that were opposite in sign those of the natural products, thereby supporting the S configuration for natural arborescidines A (1) and B (2) and the (3S,17S) configuration for natural arborescidine C (3). Our results are in agreement with the initial stereochemical assignment by Pa?s and co-workers, and are counter to their recently revised assignment. 相似文献
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The synthesis of (R)-duloxetine is described. Dynamic kinetic resolution of β-hydroxynitrile rac-1 using Candida antarctica lipase B (CALB, N435) and ruthenium catalyst 6 afforded β-cyano acetate (R)-2 in high yield and in excellent enantioselectivity (98% ee). The subsequent synthetic steps were straightforward and (R)-duloxetine was isolated in 37% overall yield over 6 steps. The synthetic route also constitute a formal total synthesis of (S)-duloxetine. 相似文献
6.
Wei Fan Lei Chen Li Hai Yong Wu~* Key Laboratory of Drug Targeting Education Ministry West China School of Pharmacy Sichuan University Chengdu China 《中国化学快报》2008,19(3)
(R)-1-(4-Methoxyphenyl)propan-2-amine 2a,an optical active intermediate for (R,R)-formoterol,was synthesized from D- alanine in 65% overall yield by using a simple route,which contained protecting amino group,cyclization,coupling with Grignard reagent,reduction and deprotection. 相似文献
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The nonproteinogenic amino acid (2R,3R)-beta-methoxytyrosine, a constituent of several cyclic depsipeptide natural products, was synthesized in protected form (8) from a readily available cinnamate ester in four steps and 62% overall yield with a greater than 28:1 er and 19:1 dr. This method provides a highly efficient, enantio- and diastereoselective synthesis of an important amino acid. 相似文献
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[reaction: see text] (-)-(6S,7S,8S,9R,10S,2'S)-Membrenone-A and (-)-(6S,7S,8S,9R,10S)-membrenone-B were prepared in 11 steps (3% and 2.4% overall yield, respectively). Key steps included a tin(II)-mediated aldol followed by a syn selective reduction, giving the C7-C9 stereocenters, a second chain extending aldol coupling, and a p-TsOH-promoted cyclization/dehydration giving the common gamma-dihydropyrone precursor. We have thus established that synthetic (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A, (-)-(6S,7S,8S,9R,10S)-membrenone-B, and (-)-(6S,7S,8S,9R,10S)-membrenone-C are the enantiomers of the natural products. 相似文献
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Tilisolol hydrochloride 1,a non-selectiveβ-adrenoceptor blocker,was developed as a drug for the treatment of hypertension and angina pectoris.The optical active forms of 1,1a and 1b were synthesized from inexpensive phthalic anhydride 2 in eight steps with 13%(S) and 15%(R) overall yield. 相似文献
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Murata K Toba T Nakanishi K Takahashi B Yamamura T Miyake S Annoura H 《The Journal of organic chemistry》2005,70(6):2398-2401
[reaction: see text] A practical and efficient total synthesis of (2S,3S,4R)-1-O-(alpha-d-galactosyl)-2-tetracosanoylamino-1,3,4-nonanetriol, OCH 1b, a potential therapeutic candidate for Th1-mediated autoimmune diseases, is described. The synthesis incorporates direct alkylation onto epoxide 5 and stereospecific halide ion catalyzed alpha-glycosidation reaction. A key intermediate 10 was obtained in only eight steps and 37% overall yield from commercially available d-arabitol 2, and the total synthesis of 1b was accomplished in 12 steps and 19% overall yield. This method will enable the synthesis of a variety of phytosphingolipids, especially that with the shorter sphingosine side chain than 1a, in a highly stereoselective manner. 相似文献
13.
The synthesis of (2R)-2-methyl-4,5-dideoxy and (2R)-2-methyl-4-deoxy analogues of 6-phosphogluconate is described. The synthetic strategy relies on the Evans aldol reaction for the installation of the chiral centres in the 2- and 3-positions. The selective phosphorylation at the primary alcohol function of (2R,3S)-3,6-dihydroxy-2-methylhexanoic acid benzyl ester (5) and (2R,3S,5S)-3,5,6-trihydroxy-2-methylhexanoic acid benzyl ester (20) was achieved with dibenzyl phosphochloridate and dibenzyl phosphoiodinate respectively, working at low temperature. (2R,3S)-3-Hydroxy-2-methyl-6-phosphonoxyhexanoic acid (9) was obtained in 25% overall yield from 4-benzyloxybutanol and (2R,3S,5S)-3,5-dihydroxy-2-methyl-6-phosphonoxyhexanoic acid (28) in 10% overall yield from L-malic acid. 相似文献
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Glycidamides 6R and 6S were elaborated to (R,R)- and (S,S)-dysibetaines (1R and 1S) by intramolecular alkylation and functional group modification in 23% overall yield. The absolute stereochemistry of natural dysibetaine was established as S,S by comparison of the optical rotation of the natural product with that of the synthetic materials. 相似文献
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The addition of 4?eq of chloral to osmundalactone (4S,5R)-4 gave quantitative formation of the hemiacetal derivative (4S,5R)-8, which was treated with methane sulfonic acid to afford the intramolecular Micheal addition product (+)-(3S,4S,5R)-9 possessing a 3,4-cis-dihydroxy-δ-lactone in 78% overall yield from (4S,5R)-4. The obtained (+)-(3S,4S,5R)-9 was subsequently converted to methyl D-digitoxoside (pyranoside) (12) in 13% overall yield and methyl D-digitoxoside (furanoside) (12) in 20% overall yield. The reaction of benzyl-osmundalactone (4R,5S)-3 and MeOH in the presence of Amberlyst A-26 as a basic catalyst gave 3,4-trans-δ-lactone (-)-(3S,4R,5S)-20 in 28% yield and 3,4-cis-δ-lactone (-)-(3R,4R,5S)-21 in 45% yield. Dibal-H reduction of (-)-(3S,4R,5S)-20 followed by catalytic hydrogenation gave L-oleandrose (6) in 86% overall yield, while Dibal-H reduction of (-)-(3R,4R,5S)-21 followed by catalytic hydrogenation provided L-cymarose (7) in 85% overall yield. 相似文献
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Conclusions A seven-stage synthesis has given optically active (2R/S, 3S, 7R/S)-2-acetoxy-3,7-dimethylpentadecane from the readily available (S)-(+)-3,7-dimethyl-1,6-octadiene, in an overall yield of 36%. The synthetic route utilizes all ten carbon atoms of the starting chiral diene.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1142–1146, May, 1988. 相似文献
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Solvolysis reaction of methyl (4S,5S)-4-(4'-methoxyphenyl)-5-tosyloxy-2(E)-hexenoate 5 in water-saturated MeNO(2) gave the 1,2-migration product, (4S,5S)-5-hydroxy-4-(4'-methoxyphenyl)-2-(E)-hexenoate 6 (55% yield), which was converted to methyl (R)-(4'-methylphenyl)hexanoate 11 in 25% overall yield (5 steps). Treatment of (R)-11 with MeLi gave tertiary alcohol congener 12, which was subjected to dehydration to afford (R)-(-)-curcumene 1. An introduction of hydroxyl group at meta-position of the aromatic ring in (R)-11 was achieved based on consecutive treatment [1) selective iodination, 2) conversion of aryl iodide to aryl boronate, 3) conversion of aryl boronate to phenol]. Thus obtained phenol (R)-16 was treated with MeLi to give tertiary alcohol congener 17, which was subjected to dehydration to afford (R)-(-)-xanthorrizol 2. 相似文献
19.
(S,R,R,S,R,S)-4,6,8,10,16,18-Hexamethyldocosane (1) was synthesized in 11% yield in 11 steps in the longest linear sequence from > or =98% pure (S)-beta-citronellal and 6 additional steps for the preparation of 11 in 23% yield from propene. Five of the six asymmetric carbon centers were generated catalytically and stereoselectively by the ZACA reaction (5 times), one lipase-catalyzed acetylation, and two chromatographic operations. 相似文献
20.
Atropisomeric (R,R)-2,2'-bi([2]paracyclo[2](5,8)quinolinophane) [(R,R)-1] and (R,R)-1,1'-bi([2]paracyclo[2](5,8)isoquinolinophane) [(R,R)-2] have been prepared in moderate overall yield (17 and 9%, respectively) by a four-step sequence starting from (R)-(-)-4-amino[2.2]paracyclophane and (R)-(-)-4-carboxy[2.2]paracyclophane, respectively. The structures have been determined on the basis of NOE (1)H NMR analysis and molecular mechanics (MM) calculations performed with a Spartan02 program, using the MMF94s force field. A preliminary, qualitative analysis of the chiroptical properties of these two compounds has also been attempted. The main spectral data can be interpreted in terms of an almost planar 2,2'-bisquinoline chromophore inserted in a paracyclophane structure in the case of (R,R)-1, while in the case of (R,R)-2, the main role is played by a distorted 1,1'-bisisoquinoline chromophore. On the basis of the above structural results, a hypothesis about the enantioselection capability of these two molecules has also been formulated. 相似文献