The structural characteristics of a mucin glycopeptide motif derived from the N-terminal fragment STTAV cell surface glycoprotein CD43 have been investigated by NMR. In this study, series molecules prepared total synthesis were examined, consisting peptide itself, three glycopeptides having clustered sites α-O-glycosylation on serine and threonine side chains with Tn, TF, STF carbohydrate antigens, respectively, one β-O-linked TF antigen. Additionally, sequence SSSAVAV, triglycosylated Ley...

Ketones undergo soft enolate formation and acylation on treatment with MgBr(2).OEt(2), i-Pr(2)NEt, various acylating agents to give 1,3-diketones. The process is particularly efficient for N-acylbenzotriazoles O-Pfp esters, and, in these cases, conducted untreated, reagent-grade CH(2)Cl(2) open the air, thus providing an exceptionally simple approach synthesis of this important class compounds.

Synthetic carbohydrate cancer vaccines have been shown to stimulate antibody-based immune responses in both preclinical and clinical settings. The antibodies observed react vitro with the corresponding natural antigens expressed on surface of tumor cells, are able mediate complement-dependent and/or antibody-dependent cell-mediated cytotoxicity. Furthermore, these proven be safe when administered patients. Until recently, only monovalent antigen constructs had prepared evaluated. Advances...

The α-alkylation of N-sulfonyl hydrazones via in situ-derived azoalkenes provides an umpolung approach to ketone that has considerable potential with regard catalysis and the direct incorporation functionality not amenable use enolate chemistry. Herein, we describe first Cu(I)-catalyzed addition Grignard reagents azoalkenes. This method is remarkable its ability deliver highly sterically hindered compounds would be difficult or impossible synthesize traditional chemistry, including those...

A broadly applicable asymmetric synthetic strategy utilizing N-amino cyclic carbamate alkylation that provides access to the various stereochemical permutations of a common structural motif found in many polycyclic polyprenylated acylphloroglucinols is described. The utility this methodology demonstrated through first total synthesis antiviral agent (+)-clusianone.

An asymmetric Mannich reaction of phenylacetate thioesters and sulfonylimines using cinchona alkaloid-based amino (thio)urea catalysts is reported that employs proximity-assisted soft enolization. This approach to enolization based on the cooperative action a carbonyl-activating hydrogen bonding moiety an amine base contained within single catalytic entity facilitate intracomplex deprotonation. Significantly, this allows over range acidity react efficiently, thereby opening door development...

Distinguishing left from right: In the title reactions, chiral N-amino cyclic carbamates (ACCs) substantially diminish drawbacks associated with use of dialkyl hydrazines, yet provide excellent stereoselectivity and high yields. addition, ACCs exhibit a unique directing effect that overrides inherent selectivity lithium diisopropylamide (LDA) enables asymmetric α,α-bisalkylation ketones (see scheme).

[reaction: see text] Simple thioesters undergo direct aldol addition to aldehydes in the presence of MgBr(2).OEt(2) and i-Pr(2)NEt using untreated, reagent-grade CH(2)Cl(2) under atmospheric conditions. The reactions proceed extremely rapidly excellent yield.

Thioesters undergo chemoselective soft enolization and acylation by N-acylbenzotriazoles on treatment with MgBr2·OEt2 i-Pr2NEt to give β-keto thioesters. Prior enolate formation is not required, the reaction conducted using untreated CH2Cl2 open air. The coupled products are stable synthetic equivalents of acids can be converted directly into esters, amides, β-diketones under mild conditions. utility this carbon−carbon bond-forming method shown through synthesis PI3-K inhibitor LY294002.

The first general method for the asymmetric α,α-bisalkylation of ketones having both α- and α'-protons is described. Both excellent regio- stereoselectivity result. transformation enabled by complex-induced syn-deprotonation (CIS-D), which completely reverses inherent preference lithium diisopropylamide (LDA) to remove less sterically hindered two similarly acidic protons. CIS-D also overrides normal tendency LDA more strongly proton in a substrate protons differing significantly their...

A new strategy for the rhodium-catalyzed enantioselective hydroacylation is described. This has been achieved through merger of iminium ion catalysis and transition-metal such that asymmetric induction derives from a readily accessible, inexpensive chiral nonracemic secondary amine catalyst rather than phosphine as typical conventional methods.

Mefloquine hydrochloride is an important antimalarial drug. It currently manufactured and administered in racemic form; however there are indications regarding the biological activity of two enantiomers that suggest superiority (+)-form. The asymmetric total synthesis (+)-enantiomer mefloquine described. key transformation utilized a novel Darzens reaction chiral α-chloro-N-amino cyclic carbamate hydrazone derived from N-amino (ACC) auxiliary.

Nonsense mutations constitute ~10% of TP53 in cancer. They introduce a premature termination codon that gives rise to truncated p53 protein with impaired function. The aminoglycoside G418 can induce readthrough and thus increase cellular levels full-length protein. Small molecule phthalimide derivatives enhance the activity have also been described. To determine whether enhancers exist among drugs are already approved for use humans, we tested seven antimalarial common R213X nonsense...

The first asymmetric total synthesis of the marine natural product apratoxin D, a highly potent inhibitor H-460 human lung cancer cell growth (IC(50) value 2.6 nM), is described. Asymmetric N-amino cyclic carbamate (ACC) α,α-bisalkylation was utilized to establish isolated C-37 methyl group with excellent selectivity. Other key transformations employed were an Evans syn-aldol and Paterson anti-aldol, both which also proceeded stereoselectivity.

Acryloyl chlorides, aldehydes, and PhSLi undergo a direct aldol cascade sequence in the presence of MgBr2 x OEt2 via situ derived thioester enolates, which is followed by oxidative elimination to give alpha-alkenyl-beta'-hydroxy thioesters. Overall, procedure rapid, efficient, generally applicable, even beta-substituted acryloyl thus providing an alternative Morita-Baylis-Hillman reaction with substantially greater synthetic scope utility.

Density functional theory calculations and experiment reveal the origin of stereoselectivity in deprotonation-alkylation chiral N-amino cyclic carbamate (ACC) hydrazones. When ACC is a rigid, camphor-derived carbamate, two conformations azaenolate intermediate differ energy due to conformational effects within oxazolidinone ring steric interactions between azaenolate. An electrophile adds selectively less-hindered π-face Although it was earlier reported that use auxiliaries led α-alkylated...

The direct addition of enolizable aldehydes and α-halo thioesters to produce β-hydroxy enabled by reductive soft enolization is reported. transformation operationally simple efficient has the unusual feature giving high syn-selectivity, which opposite that produced for (thio)esters under conventional conditions. Moreover, excellent diastereoselectivity results when a chiral nonracemic α-hydroxy aldehyde derivative used.

The first asymmetric organocatalytic sulfenylation of in situ derived nitrosoalkenes leading to chiral nonracemic α-sulfenylated ketones is described. transformation proceeds an umpolung fashion, relative enolate/azaenolate methods, and uses simple thiols, thereby obviating the need for electrophilic sulfur reagents.

(-)-A58365A (1) and (-)-A58365B (2), which are inhibitors of angiotensin-converting enzyme, were synthesized from the subunits 9 10. These coupled, resulting individual amides 17a,b converted by ozonolysis into aldehydes 18a,b, underwent cyclodehydration to enamides 19a,b. Treatment with a stannane served generate vinyl stannanes 20a,b, ketones 22a,b produced protodestannylation ozonolysis. Base treatment hydrogenolysis then afforded (1). The intermediates also 26a,b hydroboration oxidation,...

Three amino acids were converted into the derivatives 5.2 (from glycine), 6.4a and 6.4b alanine), 8.3a 8.3b O-benzyl serine). These N-alkylated acids, which can be deprotected after conversion of carboxyl an amide, correspond to general structure 2.1, a compound class use in study peptide segment coupling by ligation−acyl transfer method.