A stereodivergent synthesis of D-erythro-sphingosine and D-threo-sphingosine from L-serine

Garner, Philip

doi:10.1021/jo00253a039

Cited by 171 publications

(69 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various sphingosine stereoisomers were synthesized and purified as described previously (17)(18)(19). D-erythro-sphingosine and L-erythrosphingosine were prepared, respectively, from tert-butoxycarbonyl-Lserine and tert-butoxycarbonyl-D-serine via coupling of the Garner aldehyde (17) with lithium pentadecyne in hexamethylphosphoramidetetrahydrofuran as described by Herold (18), followed by Birch reduction in lithium-ethylamine as described by Garner (19).…”

Section: Preparation Of Sphingosine Stereoisomersmentioning

confidence: 99%

Induction of Apoptosis and Potentiation of Ceramide-mediated Cytotoxicity by Sphingoid Bases in Human Myeloid Leukemia Cells

Jarvis

Fornari

Traylor

et al. 1996

Journal of Biological Chemistry

126

View full text Add to dashboard Cite

). The present findings document the intrinsic ability of sphingoid bases to induce apoptosis in HL-60 and U937 cells. Exposure to either sphingosine or sphinganine (0.001-10 M) for 6 h promoted apoptotic degradation of genomic DNA as indicated by (a) electrophoretic resolution of 50-kilobase pair DNA loop fragments and 0.2-1.2-kilobase pair DNA fragment ladders on agarose gels, and (b) spectrofluorophotometric determination of the formation and release of double-stranded fragments and corresponding loss of integrity of bulk DNA. DNA damage correlated directly with reduced cloning efficiency and was associated with the appearance of apoptotic cytoarchitectural traits. At sublethal concentrations ( 750 nM), however, sphingoid bases synergistically augmented the apoptotic capacity of ceramide (10 M), producing both a leftward shift in the ceramide concentration-response profile and a pronounced increase in the response to maximally effective levels of ceramide. Thus, sphingosine and sphinganine increased both the potency and efficacy of ceramide. The apoptotic capacity of bacterial sphingomyelinase (50 milliunits/ml) was similarly enhanced by either (a) acute co-exposure to highly selective pharmacological inhibitors of protein kinase C such as calphostin C and chelerythrine or (b) chronic pre-exposure to the nontumor-promoting protein kinase C activator bryostatin 1, which completely down-modulated total assayable protein kinase C activity. These findings demonstrate that inhibition of protein kinase C by physiological or pharmacological agents potentiates the lethal actions of ceramide in human leukemia cells, providing further support for the emerging concept of a cytoprotective function of the protein kinase C isoenzyme family in the regulation of leukemic cell survival.Recent investigation has examined the participation of sphingophospholipid-and glycerophospholipid-derived messengers in the regulation of leukemic cell survival. We (1, 2) and others (3) have demonstrated that increased intracellular availability of ceramide induces programmed cell death or apoptosis in the human myeloid leukemia cell lines HL-60 and U937. Ceramide interacts with at least two distinct intracellular target enzymes, ceramide-activated protein kinase (4 -6) and ceramide-activated protein phosphatase (7-9). A cytotoxic role for ceramide-activated protein phosphatase and ceramideactivated protein kinase in ceramide action has been inferred, although the relative contributions of these enzymes to the initiation of apoptosis is presently uncertain (10, 11). A contrasting cytoprotective function of diglyceride and, therefore, of one or more isoforms of protein kinase C (PKC) 1 is supported by several lines of evidence. Increased intracellular availability of diglyceride abrogates the initiation of apoptotic DNA damage by ceramide in both HL-60 and U937 cells (1, 2); this effect is mimicked by such diverse pharmacological PKC activators as the stage 1 tumor promoters phorbol dibutyrate (2) and phorbol myristate acetate (2, 3), the stag...

show abstract

Section: Preparation Of Sphingosine Stereoisomersmentioning

confidence: 99%

Induction of Apoptosis and Potentiation of Ceramide-mediated Cytotoxicity by Sphingoid Bases in Human Myeloid Leukemia Cells

Jarvis

Fornari

Traylor

et al. 1996

Journal of Biological Chemistry

126

View full text Add to dashboard Cite

show abstract

“…The ethereal solution was sequentially washed with 2 N hydrochloric acid and brine, dried with sodium sulfate, and concentrated in vacuo. The residue was recrystallized from n-hexane to give 232 mg (6). p-Nitrophenyl trifluoroacetate (1.26 g, 6 mmol) was added to an ice-cooled and stirred solution of (R)-5 (232 mg, 0.67 mmol) in pyridine (2 ml).…”

Section: Determination Of the Enantiomeric Purity Of (R)-4 (S)-mtpa Cmentioning

confidence: 99%

“…3 ,4) In the same year of 1985, Kawai et al clarified the structures of the active substances produced by P. funiculosum as being four cerebrosides, Pen I-Pen IV, which were isolated in a ratio did not clearly mention the absolute configuration of Pen III, we assumed it to possess the same stereochemistry as that of Sch II. Sphingadienine B can then be dissected into two parts: aldehyde D and enyne E. Aldehyde D can be derived from L-serine (F) according to Garner et al,6) while enyne E has already been prepared by us from homoprenyl acetate (G).4) Hydroxy acid C can be prepared from stearic acid (H).…”

mentioning

confidence: 99%

Synthesis of (2S,2’R,3R,4E,8E)-N-2’-Hydroxyoctadecanoyl-1-O-(β-d-glucopyranosyl)-9-methyl-4,8-sphingadienine (Pen III), a Cerebroside Isolated fromPenicillium funiculosumas the Fruiting Inducer againstSchizophyllum commune

Abe

Mori

1994

Bioscience, Biotechnology, and Biochemistry

View full text Add to dashboard Cite

“…7=5.9 and 10.6Hz, H-l'), 2.905 (br.q, 1H, 7=4.0Hz, H-2), 2.059 (q, 2H, 7=7.1 Hz, H-6, 6' ), 1.378 (m, 2H, H-7, 7' ), 1.33-1.19 (m, 20H, -CH2-), 0.881 (t,3H,7=7.0Hz,CH2CH3). …”

mentioning

confidence: 99%

“…Compound 23E (440.0 mg) was converted into 24E (783.6 mg, 99.5%) as described -NMR of compound 24E (/J/0.37) 2H,5.428 (m,1H,2.116 (m,2H,NHCOCH2),2.028 (q,2H,7=7.1Hz,6' ), (m, 74H, -CH2-, OCH2CH3 and CHCH3), 0.880 (t,6H,7=7.0Hz,CH2CH3). Anal.…”

mentioning

confidence: 99%

Enantiospecific Syntheses of Sphingosine and Ceramide Stereoisomers with 3S Configuration from D-Glucose.

Fujita¹,

Sugimoto²,

Tomita³

et al. 1991

Agricultural and Biological Chemistry

View full text Add to dashboard Cite

A stereodivergent synthesis of D-erythro-sphingosine and D-threo-sphingosine from L-serine

Cited by 171 publications

References 0 publications

Induction of Apoptosis and Potentiation of Ceramide-mediated Cytotoxicity by Sphingoid Bases in Human Myeloid Leukemia Cells

Induction of Apoptosis and Potentiation of Ceramide-mediated Cytotoxicity by Sphingoid Bases in Human Myeloid Leukemia Cells

Synthesis of (2S,2’R,3R,4E,8E)-N-2’-Hydroxyoctadecanoyl-1-O-(β-d-glucopyranosyl)-9-methyl-4,8-sphingadienine (Pen III), a Cerebroside Isolated fromPenicillium funiculosumas the Fruiting Inducer againstSchizophyllum commune

Enantiospecific Syntheses of Sphingosine and Ceramide Stereoisomers with 3S Configuration from D-Glucose.

Contact Info

Product

Resources

About