A synthesis of protected aminoalkyl epoxides from .alpha.-amino acids

Luly, Jay R.; Dellaria, Joseph F.; Plattner, Jacob J.; Soderquist, Jeffrey L.; Yi, Nwe

doi:10.1021/jo00384a020

Cited by 207 publications

(70 citation statements)

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“…The solution was allowed to warm to room temperature and stirred for 4 hours. The reaction was then treated with saturated aqueous NH 4 Cl, extracted with CH 2 Cl 2 (2 ¥ 100 mL), dried over Na 2 SO 4 , and concentrated. Iodobenzene diacetate (8.4 g, 26.2 mmol) was then added to a solution of the crude product (3.5 g, 24 mmol) and TEMPO (0.37 g, 2.4 mmol) in CH 2 Cl 2 (50 mL).…”

Section: -Methoxymethoxy-pentanalmentioning

confidence: 99%

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Direct and Enantioselective Organocatalytic α-Chlorination of Aldehydes

2004

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Section: -Methoxymethoxy-pentanalmentioning

confidence: 99%

“…The mixture was washed with a saturated aqueous solution of Na 2 S 2 O 3 (150 mL) and extracted with CH 2 Cl 2 (2 ¥ 100 mL). The combined organics were washed with saturated aqueous NaHCO 3 (150 mL), dried over NaSO 4 …”

Section: -Methoxymethoxy-pentanalmentioning

confidence: 99%

Direct and Enantioselective Organocatalytic α-Chlorination of Aldehydes

2004

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“…, prepared as described in literature, 12,13 was oxidized to aldehyde 5 [14][15][16] (Scheme 1) with NaOCl in the presence of a catalytic amount of 4-acetamido-2,2,6,6-tetramethylpiperidin-1-yloxy radical (AcNH-TEMPO). 17,18 N-Protected α-aminoaldehydes may be prepared either by reduction of a carboxy derivative of an amino acid or by oxidation of 2-aminoalcohols, and it is known that they have a high tendency for racemization.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 2-amino alcohols and unnatural amino acids from serine

Magrioti¹,

Αντωνοπούλου²,

Pantoleon³

et al. 2003

Arkivoc

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“…The aldehyde (14), obtained via the aminoalcohol (13) 17) from 9, was treated with the ylide derived from potassium bis(trimethylsilyl)amide [[(CH 3 ) 3 Si] 2 NK] and methyltriphenylphosphonium bromide (CH 3 PPh 3 Br), to give the olefin (15). 18) Then an addition of thioacetic acid to compound 15 was carried out under ultraviolet light catalyzed conditions 19) to afford 16. The acetylsulfanylethylketone (19) that differed from intermediate (12) by the distance between the carbonyl and mercapto groups, was prepared via the a,b-unsaturated compound (18).…”

Section: -10mentioning

confidence: 99%

“…18) Then an addition of thioacetic acid to compound 15 was carried out under ultraviolet light catalyzed conditions 19) to afford 16. The acetylsulfanylethylketone (19) that differed from intermediate (12) by the distance between the carbonyl and mercapto groups, was prepared via the a,b-unsaturated compound (18). 20) Thus the aminoaldehyde (14) was transformed into the vinyl alcohol (17), which on Swern oxidation gave the corresponding a,b-unsaturated ketone (18).…”

Section: -10mentioning

confidence: 99%

Design and Synthesis of Sulfur Based Inhibitors of Matrix Metalloproteinase-1.

Fujisawa

Odake

Ogawa

et al. 2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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Fibroblast collagenase (MMP-1), a member of the matrix metalloproteinases family, is believed to be a pathogenesis of arthritis, by cleaving triple-helical type II collagen in cartilage. From the similarity of the active site zinc binding mode with hydroxamate, we designed and synthesized a a-mercaptocarbonyl possessing compounds (3-5), which incorporated various peptide sequences as enzyme recognition sites. The P 4 -P 1 peptide incorporating compound (3) exhibited as potent inhibition as the hydroxamate (1) and the carboxylate (2) type inhibitors, with an IC 50 of 10 ؊6 M order against MMP-1. But the inhibitor (3) related compounds (6-8) displayed decreased or no inhibitory potencies. These results suggest that the existence of both the carbonyl and thiol groups might be critical for the inhibition, and the distance between the two functional groups is important for inhibitory potency. For P n peptide incorporating compounds (4a-k), except for 4h and 4k, all compounds showed IC 50 values under sub-nanomolar. Among them, for potent inhibition, Leu was better than Phe and Val as the P 1 amino acid, and the P 2 position amino acid was necessary, and preferentially Phe. Insertion of the P n peptide into 4d or 4k, giving compounds 5a-c, did not increase the activities of 4d and 4k. Substitution of the mercapto group with other functional groups lost the activity of compound 4a. The stereochemical preference at the thiol-attached position was also determined by preparation of both isomers of 4a. It was found that the S configuration compound (36b) is approximately 100 times more potent than the corresponding R-isomer (36a).Key words matrix metalloproteinase; inhibitor; a-mercaptocarbonyl; isoserine; in vitro activity Design The X-ray crystal structures of MMP-1 with bound inhibitors reveal that the hydroxamate acts as a bidentate ligand with each oxygen at an optimal distance (2.1-2.2 Å) from the active-site zinc ion (structure A, Fig. 2). 13)From this structural analysis data, we reasoned that the amercaptocarbonyl group (structure B) at the cleavage site would chelate at the active-site zinc ion by both carbonyl and mercapto groups in a similar manner as the hydroxamate (Fig. 2). In comparison with the hydroxamate possessing MMPs inhibitors, little is known about thiol group including compounds. But, previously Donald and colleagues developed a b-mercapto carbonyl group possessing compound that exhibited 10 Ϫ7 M order of IC 50 against MMP-1.14) The compound differs in the distance between the carbonyl and mercapto groups from the structure B. In addition, Baxter and colleagues have prepared the thiol containing inhibitors utilizing computer-aided drug design, expecting new interactions with MMP-8 by hydrogen bonds, e.g. Ser172 of MMP-8.15) These compounds exhibited potent inhibitions with an IC 50 of 10 Ϫ7 -10 Ϫ9 M against MMP-3, -8, -9, but were not tested on MMP-1. We designed three different compounds containing an a-mercaptocarbonyl group, based on the enzyme recognition sites. The P 4 -P 1 peptide incorporati...

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A synthesis of protected aminoalkyl epoxides from .alpha.-amino acids

Cited by 207 publications

References 0 publications

Direct and Enantioselective Organocatalytic α-Chlorination of Aldehydes

Direct and Enantioselective Organocatalytic α-Chlorination of Aldehydes

Synthesis of 2-amino alcohols and unnatural amino acids from serine

Design and Synthesis of Sulfur Based Inhibitors of Matrix Metalloproteinase-1.

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