摘要：

J. CHEM. SOC. PERKIN TRANS. I 1985 2447 Total Synthesis of (*)-and (+)-Latifine Seicchi Takano," Masashi Akiyama, and Kunio Ogasawara Pharmaceutical Institute, TohokuUniversity, Aoba yama, Sendai 980,Japan Racemic latifine (+)-(1), a new representative of the rare phenolic Amaryllidaceae alkaloids, has been synthesized by employing the Claisen rearrangement of 4-benzyloxycinnamyl 2-methoxyphenyl ether (11) as a key step. Based on the racemic synthesis, (R)-(+)-latifine (R)-(1), the unnatural enantiomer, has also been synthesized from (S) -0-benzylglycidol (S) -(3) via (S)-1 -benzyloxy-3-phenylthio-propan-2-01 (S)-(4) as a key intermediate. The isolation, structure, and absolute configuration of (-)-latifine, an Amaryllidaceae alkaloid, has recently been reported by Kobayashi and co-workers.' The structure determination has revealed latifine (1) to be the first isoquinoline alkaloid possessing a 4-phenyl-5,6-dioxygenated substitution pattern and isomeric with cherylline (2) which is the only 4-phenyl-6,7-dioxygenatedisoquinoline alkaloid so far known.2 We now describe the first total synthesis of latifine (1) in racemic and unnatural enantiomeric forms as a part of our synthetic studies utilizing an optically active glycidol (hydroxymethyloxirane) deri~ative.~ The general approach which was conceived for the chiral synthesis of latifine (1) using the chiral sulphide (4) is outlined in Scheme 1.The critical feature of this plan focused upon the potential success in synthesizing the optically active allyl aryl ether (8) and its stereochemical behaviour in the Claisen rearrangement, since very few examples involving chirality transfer of chiral allyl aryl ether substrates are known.4 The availability of both enantiomers of the chiral epoxide (3) from the same precursor, D-mannitol, encouraged us to exploit this compound as the key chiral building block.' Reaction of the (S)-epoxide (S)-(3)'with sodium benzene- thiolate at 0 "Cin tetrahydrofuran (THF) smoothly gave (S)-1-benzyloxy-3-phenylthiopropan-2-ol(S)-(4) in 89% yield.Since the sulphide (S)-(4) was found to be inactive to alkylating agents under basic conditions, it was converted into the corres- ponding sulphoxide (945) upon treatment with hydrogen peroxide in aqueous methanol for 3 days at room temperature.The product (S)-(5) obtained in 100% yield appeared to be a single epimer in its chromatographic behaviour; however, its 'H n.m.r. spectrum revealed that it existed as a ca. 1:1 mixture of epimers at the newly generated sulphoxide centre. It was gratifying to find that when the sulphoxide (5) was allowed to react with 2.1 mol equiv. of n-butyl-lithium for 2 h at between -60 and 0 "C in THF containing 2.1 mol equiv. of N,N,N',N'-tetramethylethylenediamine followed by 1 mol equiv. of 4-benzyloxybenzyl chloride for 20 h at from 0 "C to room temp. it gave the alkylated product (S)-(6)as a mixture of epimers. Although both epimers could be separated on silica gel plates, the mixture gave the desired allyl alcohol (R)-(7)directly in 87% 0Bn OBn OBnQ -0 -00# HO HOOMe 1 MeoqOBn (9) Scbeme 1.yield from sulphoxide (5) as a single product upon refluxing in toluene in the presence of calcium carbonate.6 The 'H n.m.r. spectrum confirmed that compound (7) possessed the E configuration, since its olefin signals appeared at 6 5.98 and 6.58 with a coupling constant of 17.0 Hz. Having obtained the chiral allyl alcohol (R)-(7)as shown in Scheme 1, we first examined the Claisen rearrangement and the subsequent conversion into the target alkaloid using a non- chiral substrate as a model study shown in Scheme 2. Mitsunobu reaction of 4-benzyloxycinnamyl alcohol (10) and guaiacol(2-methoxyphenol)with diethyl azodicarboxylate and triphenylphosphine afforded the requisite ether (11) in 34% yield, though the yield was greatly reduced by concomitant formation of an unidentified compound which is believed to be 2448 J.CHEM. SOC. PERKIN TRANS. I 1985 OMeYOH a) (10) (111 (131 - Bn (12) Me;l Me06 IR1 (14) (15) (16 1 : R1= R2 = phthaloyl (17) : R&apo

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