An Efficient and General Enantioselective Synthesis of Sphingosine, Phythosphingosine, and 4-Substituted Derivatives

Llaveria, Josep; Dı́az, Yolanda; Matheu, M. Isabel; Castillón, Sergio

doi:10.1021/ol802379b

Cited by 65 publications

(17 citation statements)

References 59 publications

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“…Diastereoselective dihydroxylation [89% yield, 92:8 diastereomeric ratio (d.r.)] of the Z alkene delivers 22 ; it should be noted that similar functionalization of the corresponding E alkene isomer would afford an undesired diol diastereomerxxii. Dihydroxylamide 24 is secured in two steps and the target is obtained after carbohydrate deprotectionxxiii.…”

Section: Synthesis Of Natural Product Krn7000mentioning

confidence: 99%

Catalytic Z-selective olefin cross-metathesis for natural product synthesis

Meek

O’Brien

Llaveria

et al. 2011

Nature

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376

218

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Alkenes are found in a great number of biologically active molecules and are employed in numerous transformations in organic chemistry. Many olefins exist as E or higher energy Z isomers. Catalytic procedures for stereoselective formation of alkenes are therefore valuable; nonetheless, methods for synthesis of 1,2-disubstituted Z olefins are scarce. Here we report catalytic Z-selective cross-metathesis reactions of terminal enol ethers, which have not been reported previously, and allylic amides, employed thus far only in E-selective processes; the corresponding disubstituted alkenes are formed in up to >98% Z selectivity and 97% yield. Transformations, promoted by catalysts that contain the highly abundant and inexpensive molybdenum, are amenable to gram scale operations. Use of reduced pressure is introduced as a simple and effective strategy for achieving high stereoselectivity. Utility is demonstrated by syntheses of anti-oxidant C18 (plasm)-16:0 (PC), found in electrically active tissues and implicated in Alzheimer’s disease, and the potent immunostimulant KRN7000.

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Section: Synthesis Of Natural Product Krn7000mentioning

confidence: 99%

Catalytic Z-selective olefin cross-metathesis for natural product synthesis

Meek

O’Brien

Llaveria

et al. 2011

Nature

Self Cite

376

218

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“…In this study the styrenes 17a and 17b did not undergo cross metathesis reaction (Scheme 9). Since the metathesis reaction proceeds under thermodynamic control, 25 the yield and stereoselectivity of a cross metathesis reaction can be improved by increasing the equivalent of one alkene and the reaction time. Thus, from our previous experiences, 17a,b,c,f the best results were obtained when the ratios 3 : 16 = 2 : 1, 14 : 16 = 2 : 1 and 17c-i : 16 = 4 : 1 were maintained to obtain exclusively E isomer in all the cases (Table 1).…”

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confidence: 99%

Diastereoselective one-pot Wittig olefination–Michael addition and olefin cross metathesis strategy for total synthesis of cytotoxic natural product (+)-varitriol and its higher analogues

et al. 2011

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A stereoselective route for the total synthesis of anticancer marine natural product (+)-varitriol (1) is detailed herein. The impressive biological activity and interesting structural features of natural (+)-varitriol fuelled us to undertake the synthesis of some higher analogues (1a-j) of this molecule. The key features of the synthetic strategy include one-pot Wittig olefination followed by a highly diastereoselective oxa-Michael addition to assemble stereochemically pure tetrasubstituted THF moiety of the natural varitriol and olefin cross metathesis to couple the aromatic part with tetrasubstituted THF moiety. The total synthesis of title natural product is efficient with 21.8% overall yield for 9 linear steps from D-ribose and thus facilitates the more scaled-up practical route for the synthesis of 1 and its analogues as well. The synthetic (+)-varitriol (1) and its analogues were screened for their cytotoxicity. The present synthetic approach paves the way for preparation of numerous analogues of the title natural product for drug development.

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“…Synthesis of compound 7 from racemic butadiene monoepoxide (5). [29] ence of the second generation Grubbs catalyst to afford compound 7 in excellent yield (99 %) and stereoselectivity, with only the E isomer being detected by 1 H NMR spectroscopy.…”

Section: Resultsmentioning

confidence: 99%

“…We have described the substrate-controlled dihydroxylation of compound 7 by using osmium catalysis, which provides a separable mixture of 8 and 9 in a 3.3:1 ratio. [29] The diastereomeric ratio was further improved by using (DHQ) 2 PYR as a ligand. Under these conditions, the reaction was quantitative, and the ratio 8/9 was improved to 5.2:1, which allowed the isolation of compound 8 in an 80 % yield over three steps (Scheme 4).…”

Section: Resultsmentioning

confidence: 99%