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 (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 (1R,2S,3R)-2-acetyl-4-(1,2,3,4-tetrahydroxybutyl)thiazole

Two different methods for preparing the thiazole analogue 3 of the biologically active compound (1R,2S,3R)-2-acetyl-4(5)-(1,2,3,4- tetrahydroxybutyl)imidazole 1 are reported.     

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.     

Asymmetric synthesis of (6R)-4-hydroxy-6-substituted-δ-lactones

A novel approach for the asymmetric synthesis of (6R)-4-hydroxy-6-substituted-δ-lactones has been achieved using asymmetric reduction of a prochiral ketone in the presence of (S)-(?)-diphenyl-prolinol/borane as a key step. The enantiomeric purity of the products was determined by chiral GC.     

(R)-3,3-二甲基-2-羟基-4-氧代丁酸乙酯的不对称合成

研究了异丁醛与乙醛酸乙酯不对称羟醛缩合反应合成(R)-3,3-二甲基-2-羟基-4-氧代丁酸乙酯,考察了催化剂种类及用量、反应时间、反应溶剂对羟醛缩合反应的影响。确定较佳反应条件为:L-组氨酸作催化剂,用量为乙醛酸乙酯物质的量的30%,乙二醇为溶剂,反应时间24h。(R)-3,3-二甲基-2-羟基-4-氧代丁酸乙酯的收率达75%,ee值为73%。产物结构经1H NMR,GC-MS进行了表征。     

Asymmetric transfer hydrogenation of 2-tosyloxy-1-(4-hydroxyphenyl)ethanone derivatives: synthesis of (R)-tembamide, (R)-aegeline, (R)-octopamine,and (R)-denopamine

Catalytic transfer hydrogenation of 2-tosyloxy-1-(4-hydroxyphenyl)ethanone derivatives leads to efficient synthesis of β-adrenergic agonists, (R)-tembamide, (R)-aegeline, (R)-octopamine, and (R)-denopamine.     

Chemoenzymatic synthesis of (3R,4S)- and (3S,4R)-3-methoxy-4-methylaminopyrrolidine

An efficient and a convenient enantioselective synthesis of (3R,4S)-3-methoxy-4-methylaminopyrrolidine has been carried out by a lipase-mediated resolution protocol. This method describes the preparation of (±)-1-Cbz-cis-3-azido-4-hydroxypyrrolidine starting from commercially available diallylamine followed by ring-closing metathesis (RCM) via S_N2 displacement reactions. Pseudomonas cepacia lipase immobilized on diatomaceous earth (Amano PS-D) provides (3R,4S)-11 and (3S,4R)-12 in an excellent enantiomeric excess.     

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.     

(R)-4-Menthenone in the synthesis of optically pure sex pheromone of the peach leafminer moth (Lyonetia clerkella)

The synthesis of (14S)-methyloctadec-1-ene, sex pheromone of the peach leafminer moth (Lyonetia clerkella), is described to demonstrate a new potential of the synthetic use of (R)-4-menthenone.     

Total synthesis of (3R, 4S)-4-hydroxylasiodiplodin

Abstract

An alternative and concise total synthesis of (3?R, 4S)-4-Hydroxylasiodiplodin has been reported from inexpensive and commercially available 6-heptenal and Orsellinic acid starting materials. The key steps involved in the synthesis are Wittig reaction, Sharpless epoxidation, Yamaguchi esterification and ring-closing metathesis (RCM).     

Asymmetric Synthesis of (-)-(2R,3R,6S)-Irnigaine

Introduction　　Asarelativelynewmemberofnaturalalkaloidswith2 ,6 disubstituted 3 piperidinolskeleton ,irnigaine 1wasisolatedfromthetubersofArisarumVulgare (Araceae)in1995byMelhaouiandBode .1Itsstructureandrelativeconfigurationswereelucidatedby1HNMRstudiesandtheabsoluteconfigurationwasproposedonthebasisofitsopti calrotation .1Soonafterthen ,Meyerandhisco workersreportedthefirstsynthesisof (- ) (2R ,3R ,6S) irni gaineandtheconfigurationconfirmation .Althoughtheirsynthesisroutewasshortan…     

Asymmetric synthesis of (R)-(+)- and (S)-(-)-2,2,4-trimethyl-4-(hydroxymethyl)-1,3-dioxolane of high enantiomeric purity

The title compounds, $\text{1}$ and $\text{1}$', are readily available in four steps from 2-benzyloxymethyl-2-propen-1-ol, the key step being Sharpless asymmetric epoxidation to give the chiral epoxides $\text{5}$ or $\text{5}$'. The total chemical yield of $\text{1}$ or $\text{1}$' is 50%, the final products being obtained essentially optically pure. By suitable protecting group manipulation, both title enantiomers can be produced from either of the antipodal epoxides $\text{5}$ or $\text{5}$'.     

Convenient synthesis of （2S,3R,4R,5S,6R）-2-（3-（4-ethylbenzyl）-4- chlorophenyl）-6-（hydroxymethyl）-tetrahydro- 2H-pyran-3,4,5-triol

A convenient approach for the preparation of （2S,3R,4R,5S,6R）-2-（3-（4-ethylbenzyl）-4-chlorophenyl）-6-（hydroxymethyl）- tetrahydro-2H-pyran-3,4,5-triol I is developed. The target compound via four steps is synthesized from 4-bromo-2-（bromomethyl）- 1-chlorobenzene and the isomers of undesired ortho-products were avoided during the preparation.     

Asymmetric syntheses of (1r,3R,4S)- and (1s,3R,4S)-(3,4-difluorocyclopentyl)-alanine derivatives

By employing a sequence of epoxide opening, asymmetric alkylation, and fluorination, polyfluorinated cyclopentylamino acids with defined stereochemistries were prepared.     

Asymmetric synthesis of L-carnitine from (R)-3-chloro-1,2-propanediol

A practical chemical synthesis of L-carmtine(1) has been accomplished from(R)-3-chloro-1,2-propanediol((R)-4),which is a main by-product originated from(R,R)-Salen Co(Ⅲ) catalyzed hydrolytic kinetic resolution(HKR) of(±)-epichlorohydrin.(R)-4 was utilized as a chiral starting material to prepare the key intermediate cyclic sulfite((R)-S).The new synthetic approach demonstrated an efficient utilization of organic by-product for the asymmetric synthesis of bioactive compounds.     

Asymmetric synthesis of Goniothalesdiol A from (R)-2,3-O-cyclohexylidine glyceraldehyde

Goniothalesdiol A 1 has been synthesized from (R)-2,3-O-cyclohexylidine glyceraldehyde with high stereoselectivity and 22% overall yield in 11 simple steps. The key features of the synthetic strategy include the stereocontrolled allylation of (R)-2,3-O-cyclohexylidine glyceraldehydes; the cross-metathesis with a Grubbs’s second generation catalyst, and the intramolecular base-catalyzed oxy-Michael addition for the formation of the tetrahydropyran ring.