41365-75-7Relevant articles and documents
Synthetic studies on statins. Part 1: A short and cyanide-free synthesis of atorvastatin calcium via an enantioselective aldol strategy
Hu, Lemeng,Xiong, Fangjun,Chen, Xiaofei,Chen, Wenxue,He, Qiuqin,Chen, Fener
, p. 207 - 211 (2013/04/10)
A short and cyanide-free enantioselective synthesis of atorvastatin calcium has been achieved starting from a commercially available highly substituted 1,4-diketone in an overall yield of 40%. The key step in this approach is the asymmetric aldol reaction of an aldehyde with diketene in the presence of Ti(O-i-Pr)4-Schiff base complex to create the (5R)-stereochemistry of atorvastatin calcium.
The importance of the amide bond nearest the thiol group in enzymatic reactions of coenzyme A
Xun, Jin,Huang, Haidong,Vogel, Kurt W.,Drueckhammer, Dale G.
, p. 90 - 107 (2007/10/03)
Analogues of coenzyme A (CoA) and of CoA thioesters have been prepared in which the amide bond nearest the thiol group has been modified. An analogue of acetyl-CoA in which this amide bond is replaced with an ester linkage was a good substrate for the enzymes carnitine acetyltransferase, chloramphenicol acetyltransferase, and citrate synthase, with Km values 2- to 8-fold higher than those of acetyl-CoA and Vmax values from 14 to >80% those of the natural substrate. An analogue in which an extra methylene group was inserted between the amide bond and the thiol group showed less than 4-fold diminished binding to the three enzymes but exhibited less than 1% activity relative to acetyl-CoA with carnitine acetyltransferase and no measurable activity with the other two enzymes. Analogues of several CoA thioesters in which the amide bond was replaced with a hemithioacetal linkage exhibited no measurable activity with the appropriate enzymes. The results indicate that some aspects of the amide bond and proper distance between this amide and the thiol/thioester moiety are critical for activity of CoA ester-utilizing enzymes.
Bifunctional polyethylene glycol derivatives
-
, (2008/06/13)
The present invention provides novel heterobifunctional and monobifunctional polyethylene glycol derivatives for the pegylation of therapeutically active proteins. The heterobifunctional PEGs which bear two different functional groups as well as the monobifunctional PEGs which contain two similar functional groups, may be used for cross-linking purposes. The cross-linking may be intramolecular between two areas within the same molecule or intermolecular between two separate molecules. The pegylated protein conjugates that are produced, retain a substantial portion of their therapeutic activity and are less immunogenic than the protein from which the conjugate is derived. New syntheses for preparing such bifunctional derivatives are described.
Tricyclic CNS active agents by intramolecular Oxa-Pictet-Spengler reaction
Wunsch,Zott,Hofner,Bauschke
, p. 487 - 495 (2007/10/02)
Mitsunobu inversion of the (S)-configurated lactate (S)-7, which is prepared in four steps starting from (S)-tyrosine, leads to the (R)-configurated lactate (R)-7. The key step in the transformation of the enantiomeric lactates (S)-7 and (R)-7 into the benzomorphan analogous tricycles (R,S)-16a,b, (S,R)-16a,b, (S,S)-22, and (R,R)-22 is an intramolecular Oxa-Rictet-Spengler reaction: The amides (S)-13, (R)-13, (S)-19 and (R)-19, in which the carbonyl moiety - masked as an acetal - is linked to the 2-phenylethanol moiety, are cyclized to give the tricyclic amides (R,S)-15, (S,R)-15, (S,S)-21, and (R,R)-21, respectively. In a concentration of 100 μM both enantiomers of 16a, 16b, and 22 are not able to compete with 3H-(+)-MK 801 for the phencyclidine binding sites of NMDA receptors. In vivo, only (R,S)-16b and (S,S)-22 exhibit weak sedative and analgesic activity.
Tricyclic benzomorphan analogues by intramolecular Oxa-Pictet-Spengler reaction
Wunsch,Zott
, p. 2307 - 2310 (2007/10/02)
The key step in the regio- and stereoselective preparation of the benzomorphan analogues 9, 10a, 10b, 14 and 15 is an intramolecular Oxa-Pictet-Spengler reaction. Masked as an acetal the carbonyl component is connected via an amide to the 2-phenylethanol component (7, 12).
Use of oxidized polyamines, especially NN'-bis-(3-propionaldehyde)-1-4-diaminobutane (spermine dialdehyde) as immunosuppressive agents
-
, (2008/06/13)
This invention relates to the use of oxidized polyamines, and especially aminoaldehydes such as spermine bisaldehyde both in vitro and in vivo to elicit an immunosuppressive response in living cells. It also relates to the therapeutic application of these compounds to induce an immunosuppressive response in living organism.
Fructose 1,6-Diphosphate Aldolase Catalyzed Stereoselective Synthesis of C-Alkyl and N-Containing Sugars: Thermodynamically Controlled C-C Bond Formations.
Durrwachter, John R.,Wong, Chi-Huey
, p. 4175 - 4181 (2007/10/02)
Fructose 1,6-diphosphate aldolase catalyzed aldol condensations have been used in syntheses of several new N-containing and C-alkyl sugars on 4-20 mmol scales.The enzyme is highly specific for dihydroxyacetone phosphate as donor but accepts a number of achiral and chiral aldehydes (both D and L isomers) as acceptors.Due to the reversible nature of the aldol reaction, a thermodynamically controlled approach was employed for the syntheses in which racemic aldehydes were used as substrates and thermodynamically more stable products were preferentially produced.
