Search

Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC 50 values between 30-100 nM. Potency is strongly controlled by substitution on both rings and the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity and chain-length factors provide the greatest inhibitory potency. Structural comparisons based on 3D shape analysis and electrostatic complementarity support this conclusion. The antagonists are neuroprotective in both in vitro and in vivo models of ischemic cell death. In addition, some compounds exhibit anticonvulsant properties. Unlike earlier generation NMDA receptor antagonists and some NR2B-selective antagonists, the present series of propanolamines does not cause increased locomotion in rodents. Thus, the NR2B-selective antagonists exhibit a range of therapeutically interesting properties.

The screening of 310 microbial strains yielded eight as suitable biocatalysts for the asymmetric bioreduction of a highly hindered bisaryl ketone to its corresponding alcohols. The production of both enantiomers with elevated optical purity (ee>96%) was achieved by different microorganisms. When scaling up the asymmetric bioreduction process in laboratory bioreactors (23 l scale), the production of preparative amounts (1.5 g) of the ( S ) enantiomer with elevated optically purity (ee>96%) was achieved when employing the yeast Rhodotorula pilimanae ATCC 32762. Achieving this asymmetric bioreduction with enantiocomplementarity in employing such a hindered substrate is remarkable and highlights the potential of such biological approach.

A highly convergent, asymmetric synthesis of L-768,673, an I ks Class III antiarrythmic drug candidate, is described. Synthesis of the recemic 1-trifluoroethyl-3-amino-5-phenyl benzodiazepinone [(±)-amine] was achieved by Ru-catalyzed hydrogenation of the corresponding oxime that was derived from commercially available 1-trifluoroethyl-5-phenyl benzodiazepine in 76% overall yield. An efficient one-pot resolution-racemization of (±)-amine provided the desired (±)-amine as its mandelate salt in 92% yield and 99.4% ee. Regioselective ortho-lithiation of 1,3-bis(trifluoromethyl)benzene with n-BuLi in the presence of a catalytic amount of 2,2′,6,6′-tetramethylpiperidine afforded its aryl lithium. Subsequent transmetalation and alkylation with allyl bromide produced the corresponding olefin. Ru-catalyzed oxidative cleavage of the terminated double bond of the olefin provided the desired 2,4-bis(trifluoromethyl)phenylacetic acid in 35% overall yield. A modified Schotten-Baumman procedure was developed for coupling of (+)-amine and the acid to produce L-768,673 in 92% yield without racemization.

The dramatic difference in reactivity of the two diastereomeric acid esters 4A and 4B during decarboxylation has been thoroughly investigated. The (R) isomer 4A underwent decarboxylation to provide a 94:6 mixture of SA and 5B at 80 "C in 5-6 h. Under the same conditions the (S) isomer 4B did not undergo decarboxylation and with further heating to 120 "C gave mainly the ring-opened decomposition product 6 along with unidentified decomposition products. A mechanistic rationale for this unusual reactivity profile is provided.

The synthesis of 1 was accomplished in 55% overall yield via the Pd-catalyzed coupling of 3 and 4 followed by Cu-catalyzed cyclization of the resulting intermediate 2.

Two approaches for the asymmetric preparation of (−)- or (+)- α-aminobenzlactam 1 are described. One route is based on the asymmetric hydrogenation of enamide 5 and the other on the racemization/resolution of (±)- 1 .

A series of 5-substituted uracil and cytosine dioxolanyl nucleosides were synthesized as potential anti-HIV agents. Compounds 3a and 3c were found to be extremely in acutely infected human lymphocytes.

A series of 5-substituted uracil and cytosine dioxolanyl nucleosides were synthesized as potential anti-HIV agents. Compounds 3a and 3c were found to be extremely in acutely infected human lymphocytes.

The synthesis of 1 was accomplished in 55% overall yield via the Pd-catalyzed coupling of 3 and 4 followed by Cu-catalyzed cyclization of the resulting intermediate 2.

The dramatic difference in reactivity of the two diastereomeric acid esters 4A and 4B during decarboxylation has been thoroughly investigated. The (R) isomer 4A underwent decarboxylation to provide a 94:6 mixture of SA and 5B at 80 "C in 5-6 h. Under the same conditions the (S) isomer 4B did not undergo decarboxylation and with further heating to 120 "C gave mainly the ring-opened decomposition product 6 along with unidentified decomposition products. A mechanistic rationale for this unusual reactivity profile is provided.

A practical synthesis of nicotinamide mononucleotide (β-NMN) and a high yield coupling with AMP-morpholidate that also provides NAD+ in an efficient manner are reported.

When lithium enolates are allowed to react with selenium metal, selenolate (selenide) ions are formed. Alkylation of these selenolate ions produces the corresponding α-alkylselenenyl carbonyl derivatives. These derivatives can then be converted to their unsaturated counterparts using the same type of protocols that are employed with arylselenenyl derivatives.

Investigation into the selectivity observed in the synthesis of 1β-me- thylcarbapenems was carried out by examining (1) the rotational barrier between the two possible ketene acetal conformations A and B and (2) the protonation of ketene acetal 3 to the mono acid product 2, using the MNDO Hamiltonian

(·4H2O) [304-59-6] C4H4KNaO6 (MW 210.17) InChI = 1S/C4H6O6.K.Na/c5-1(3(7)8)2(6)4(9)10;;/h1-2,5-6H,(H,7,8)(H,9,10);;/q;2*+1/p-2 InChIKey = LJCNRYVRMXRIQR-UHFFFAOYSA-L [6381-59-5] C4H12KNaO10 (MW 282.25) InChI = 1S/C4H6O6.K.Na.4H2O/c5-1(3(7)8)2(6)4(9)10;;;;;;/h1-2,5-6H,(H,7,8)(H,9,10);;;4*1H2/q;2*+1;;;;/p-2 InChIKey = VZOPRCCTKLAGPN-UHFFFAOYSA-L (chelating agent for metal ions) Alternate Names: Rochelle salt; Seignette salt. Physical Data: tetrahydrate:1c mp 70–80 °C; loses 3H2O at 100 °C; becomes anhydrous at 130–140 °C; dec 220 °C; d 1.79 g cm−3. The physicochemical properties of this tartrate salt are well documented.1b Solubility: (g 100 mL−1 H2O) 42 at 0 °C, 82 at 16 °C, 140 at 29 °C, 225 at 40 °C;11 insol alcohol. Form Supplied in: the tetrahydrate is widely available as translucent crystals or as a white crystalline solid. Analysis of Reagent Purity: by nonaqueous titration.2 Purification: can be recrystallized from a chilled solution of distilled H2O.3 Handling, Storage, and Precautions: purgative; reactions should be performed in a well-ventilated fume hood.

An efficient synthesis of a key intermediate 2a for the synthesis of 2-functionalized methyl-1β-methylcarbapenem antibiotics 1 has been realized via a stereoselective decarboxylation reaction.

A total synthesis of the three anti-coccidial agents WS-5995 A, B, and C by a Diels-Alder route is described. An intramolecular lactonization involving the displacement of a chlorine atom on a naphthoquinone was the key step in the synthesis of A.