Alkylation of camphor imines of glycinates. Diastereoselectivity as a function of electronic factors in the alkylating agent

1986 ◽  
Vol 64 (4) ◽  
pp. 726-731 ◽  
Author(s):  
John M. McIntosh ◽  
Pratibha Mishra
Keyword(s):  
Transition State ◽  
Alkylating Agent ◽  
Alkylating Agents ◽  
Type Systems ◽  
Alkyl Halides ◽  
State Interaction ◽  
Tert Butyl ◽  
Ca 50

Alkylation of the (R)-camphor imine of tert-butyl glycinate with a variety of alkylating agents gave diastereoselectivities ranging from 0–100%. Simple alkyl halides larger than methyl give de's (diastereomeric excesses) of ca. 50% whereas those derived from allylic type systems afford de's of 75–100%. The results are best explained by invoking a transition state interaction between the π system of the alkylating agent and the imine which, for steric reasons, requires alkylation to occur from the pro-R face.

Heterocyclic ambident nucleophiles. II. The alkylation of adenine

1981 ◽  
Vol 34 (5) ◽  
pp. 1107 ◽  
Author(s):  
AE Beasley ◽  
M Rasmussen
Keyword(s):  
Transition State ◽  
Alkylating Agent ◽  
Alkyl Halides ◽  
Transition State Structures

The alkylation of un-ionized adenine by a variety of primary alkyl halides under standardized, common conditions (HCONMe2, 100�) was investigated. The alkylation pattern (N 1 : N 3 : N 7 : N 9) was found to be relatively insensitive to changes in the nature of the alkylating agent, except for cases involving benzyl chloromethyl ether and chloromethyl pivalate. An interpretation of these patterns in terms of modern ambient nucleophile reactivity concepts and variable SN2 transition state structures is presented.

New sterically hindered bis-catechol, bis- o -quinone and its bis-triphenylantimony(v) bis-catecholate. 3,5-Di- tert -butyl-6-methoxymethylcatechol as alkylating agent

2018 ◽  
Vol 28 (1) ◽  
pp. 76-78 ◽  
Author(s):  
Maxim V. Arsenyev ◽  
Tatyana V. Astafeva ◽  
Evgeny V. Baranov ◽  
Andrey I. Poddelsky ◽  
Sergey A. Chesnokov
Keyword(s):  
Alkylating Agent ◽  
Tert Butyl ◽  
Sterically Hindered

Hydroxamic acids. V. The alkylation of O-alkylarylhydroxamic acids

1974 ◽  
Vol 27 (6) ◽  
pp. 1341 ◽  
Author(s):  
PM Beart ◽  
AD Ward
Keyword(s):  
Spectral Data ◽  
Alkylating Agent ◽  
Alkylating Agents ◽  
Hydroxamic Acids ◽  
Aryl Ring ◽  
Independent Synthesis ◽  
Unambiguous Assignment

The reactions of O-alkylarylhydroxamic acids with a variety of alkylating agents, to yield mixtures of the N,O-dialkyl and 0,O'-dialkyl products, are described. Spectral data and independent synthesis allow the unambiguous assignment of structure to these isomeric products. Substituents on the aryl ring exert an electronic influence on the ratio of the two products; the extent of this influence varies with the alkylating agent. Diazomethane, triethyloxonium tetrafluoroborate and methyl fluorosulphonate give largely, but not exclusively, the 0,O'-dialkyl product. Methyl fluorosulphonate, in the presence of a base, reacts further to form an unstable salt which appears also to function as an alkylating agent.

scholarly journals Endotoxin Stimulation in Patients With Lymphoma: Correlation With the Myelosuppressive Effects of Alkylating Agents

Blood ◽  
1972 ◽  
Vol 39 (5) ◽  
pp. 602-609 ◽  
Author(s):  
Ronald C. DeConti ◽  
Stephen R. Kaplan ◽  
Paul Calabresi
Keyword(s):  
Bone Marrow ◽  
Hodgkin's Disease ◽  
Alkylating Agent ◽  
Hodgkin’S Disease ◽  
Alkylating Agents ◽  
Previous Therapy ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Made In

Abstract Estimates of the bone marrow granulocyte reserve were made in 97 patients with lymphoma utilizing the endotoxin Pyrexal. Normal granulocyte responses were observed in most patients who had not received prior myelosuppressive therapy. Patients with lymphosarcoma responded as well as those with Hodgkin’s Disease. All patients with leukopenia due to previous therapy or marrow infiltration failed to respond. In the absence of leukopenia only 47% of previously treated patients achieved normal responses. The severity of granulocytopenia produced by intravenous alkylating agent therapy was correlated with pretreatment Pyrexal responses. Patients with normal granulocyte reserves, as demonstrated by this test, tolerated subsequent chemotherapy with significantly less severe granulocytopenia (p <0.02) than patients with abnormal test responses. Nadir granulocyte values below 1000 cells/cu mm developed in 7 of 33 patients with normal Pyrexal responses and in 11 of 15 abnormal responders, despite comparable pretreatment granulocyte values.

Ambident Heterocyclic Reactivity: Alkylation of 4-Substituted and 2,4-Disubstituted Benzimidazoles

1994 ◽  
Vol 47 (8) ◽  
pp. 1523 ◽  
Author(s):  
MR Haque ◽  
M Rasmussen
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Electrostatic Field ◽  
Transition States ◽  
Alkyl Halides ◽  
Methyl Group ◽  
Site Selectivity ◽  
Leaving Group ◽  
Standard Set ◽  
Specific Association

The N1/N3-alkylation patterns of 4-amino-, 4-methyl- and 4-nitro-benzimidazole anions, and their 2-methyl analogues, with a standard set of primary alkyl halides (in dimethylformamide, 30°) have been determined and compared. The observed regioselectivities are dominated by proximal effects-electrostatic field, non-bonded steric and in some cases specific association (hydrogen bonding)-the interplay of which is critically dependent on the (variable) geometries of the SN2 transition states involved, in particular on the N---C distance of the developing N-alkyl bonds. The presence of a symmetrically placed 2-methyl group produces an enhanced N1/N3 site selectivity, very sensitive to the loose-tight nature of the transition state. Halide leaving group effects on butylation regioselectivities of 2-unsubstituted, 2-ethoxy-, 2-methyl- and 2-chloro-4-methylbenzimidazole anions, whilst small, are consistent with a Bell-Evans-Polanyi analysis of SN2 transition state variations, with the earlier transition states of CH3(CH2)3I leading to reduced regioselectivities.

SOME DEUTERIUM KINETIC ISOTOPE EFFECTS: IV. β-DEUTERIUM EFFECTS IN WATER SOLVOLYSIS OF ETHYL, ISOPROPYL, AND tert-BUTYL COMPOUNDS

1960 ◽  
Vol 38 (11) ◽  
pp. 2171-2177 ◽  
Author(s):  
K. T. Leffek ◽  
J. A. Llewellyn ◽  
R. E. Robertson
Keyword(s):  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Isotope Effects ◽  
Kinetic Isotope Effects ◽  
Alkyl Halides ◽  
Tert Butyl ◽  
Kinetic Isotope ◽  
Deuterium Isotope Effects ◽  
Intramolecular Forces

The secondary β-deuterium isotope effects have been measured in the water solvolytic reaction of alkyl halides and sulphonates for primary, secondary, and tertiary species. In every case the kinetic isotope effect was greater than unity (kH/kD > 1). This isotope effect may be associated with varying degrees of hyperconjugation or altered non-bonding intramolecular forces. The experiments make it difficult to decide which effect is most important.

scholarly journals Evaluation of extracorporeal alkylation of red cells as a potential treatment for sickle cell anemia

Blood ◽  
1976 ◽  
Vol 47 (3) ◽  
pp. 481-488 ◽  
Author(s):  
S Charache ◽  
R Dreyer ◽  
I Zimmerman ◽  
CK Hsu
Keyword(s):  
Cell Survival ◽  
Alkylating Agent ◽  
Nitrogen Mustard ◽  
Alkylating Agents ◽  
Red Cells ◽  
Red Cell ◽  
Cell Life ◽  
Red Cell Survival ◽  
Toxic Reactions ◽  
Unacceptable Toxicity

Abstract Nitrogen mustard and nor-nitrogen mustard inhibit sickling, but the concentrations required would be associated with unacceptable toxicity if these agents were administered to patients. Red cells could be treated extracorporeally and infused back into donors, if the alkylating agent could be removed or inactivated, if the treatment per se did not significantly shorten red cell survival, and if viable alkylated lymphocytes could be eliminated from the treated blood. To estimate whether these conditions could be met in a clinical trial, red cells from four dogs were alkylated at 6-wk intervals. No toxic reactions were observed, although not all nor-nitrogen mustard was removed by the washing procedure. Red cell survival was shortened to about half that of control cells, using concentrations of alkylating agent which reduce sickling by 50%. Lymphocytes from treated blood could still exclude trypan blue, but could not be shown to circulate after reinfusion into donor dogs. If alkylating agents are used to treat patients' cells, inhibition of sickling may outweigh the shortening of red cell life span induced by the treatment; blood should probably be irradiated before infusion to avoid administration of alkylated and potentially mutated, but viable, lymphocytes.

Single, sequential, and multiple alkylating agent therapy for multiple myeloma: a CALGB Study.

1986 ◽  
Vol 4 (9) ◽  
pp. 1331-1339 ◽  
Author(s):  
M R Cooper ◽  
O R McIntyre ◽  
K J Propert ◽  
S Kochwa ◽  
K Anderson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Alkylating Agent ◽  
Alkylating Agents ◽  
Single Agent ◽  
Cost Savings ◽  
Initial Therapy ◽  
Myeloma Protein ◽  
Fourth Group ◽  
To Receive ◽  
Agent Treatment

Four intravenous (IV) alkylating agent regimens were tested in 615 previously untreated patients with multiple myeloma. Patients were randomized to receive melphalan, cyclophosphamide, and carmustine in combination (MCBP), sequentially (Seq-MCBP), or in combination with doxorubicin (MCBPA). The fourth group received IV melphalan (MP) as the only alkylating agent. All groups received a tapering dose of prednisone. Toxicity was similar for all regimens although the nadir of cytopenia was reached more quickly for the regime including melphalan only. Response as measured by reduction in myeloma protein or other parameters were similar for the four treatments. Survival was significantly poorer for the group receiving the alkylating agents in sequence. The survival of high tumor cell load patients who were azotemic was better in the groups treated with IV MP or with the combination of IV MCBP. In view of the simplicity and probable cost savings attached to single-agent treatment, a melphalan/prednisone regimen should be considered as initial therapy for all patients with myeloma.

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