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Peter D Johnson

Publications and source records attributed to Peter D Johnson.

6 recordsLinked to original sources

Synthesis of C-15 vindoline analogues by palladium-catalyzed cross-coupling reactions.

Described are general protocols for the rapid construction of various C-15-substituted analogues of vindoline using palladium-catalyzed cross-coupling reactions. The required bromo- and iodovindolines were prepared in high yield by the reaction of vindoline with N-bromosuccinimide or N-iodosuccinimide, respectively. The study not only led to the preparation of a number of structurally novel vindoline analogues but also opens the door to new strategies for the synthesis of vinblastine, vincristine, and related anticancer agents. Also described is the conversion of ent-tabersonine to ent-vindoline.

Antineoplastic Agents↗

Concise and enantioselective synthesis of the aminocyclitol core of hygromycin A.

[reaction: see text] Stereoselective aminohydroxylation and dihydroxylation using osmium(VIII) oxidants enabled the short and efficient synthesis of the aminocyclitol core of hygromycin A. In addition to allowing the selective introduction of the heteroatoms N and O, the use of osmium (via an osmate ester) as a protecting group for a 1,2-glycol is also reported. This tactic allowed efficient differentiation of otherwise equivalent hydroxyl groups and allowed us to complete the synthesis in short order (14 steps) and excellent overall yield (12%).

Cinnamates↗

The tethered aminohydroxylation (TA) reaction.

Since Sharpless' discovery of the asymmetric aminohydroxylation (AA) reaction, a major challenge for chemists has been to find ways of controlling the regio- and stereochemical outcome of this important reaction. Detailed herein is a review of our novel approach towards gaining reliable and predictable regio- and stereocontrol through the use of a tethered carbamate to promote an intramolecular AA reaction, along with a description of the mechanism proposed for this new methodology.

Journal Article↗

The tethered aminohydroxylation (TA) of cyclic allylic carbamates.

The tethered aminohydroxylation of cyclic allylic carbamates is described using catalytic amounts of potassium osmate. The mechanism of reaction involves formation of an imido-osmium complex which adds intramolecularly to alkenes with complete control of both regio- and stereoselectivity: the formation of syn-aminodiol motifs is now straightforward using this chemistry. Proof of the mechanism was obtained with an X-ray crystal structure of an azaglycolate osmate ester intermediate.

Journal Article↗

Comparing computer-interpretable guideline models: a case-study approach.

OBJECTIVES: Many groups are developing computer-interpretable clinical guidelines (CIGs) for use during clinical encounters. CIGs use "Task-Network Models" for representation but differ in their approaches to addressing particular modeling challenges. We have studied similarities and differences between CIGs in order to identify issues that must be resolved before a consensus on a set of common components can be developed. DESIGN: We compared six models: Asbru, EON, GLIF, GUIDE, PRODIGY, and PROforma. Collaborators from groups that created these models represented, in their own formalisms, portions of two guidelines: American College of Chest Physicians cough guidelines [correction] and the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. MEASUREMENTS: We compared the models according to eight components that capture the structure of CIGs. The components enable modelers to encode guidelines as plans that organize decision and action tasks in networks. They also enable the encoded guidelines to be linked with patient data-a key requirement for enabling patient-specific decision support. RESULTS: We found consensus on many components, including plan organization, expression language, conceptual medical record model, medical concept model, and data abstractions. Differences were most apparent in underlying decision models, goal representation, use of scenarios, and structured medical actions. CONCLUSION: We identified guideline components that the CIG community could adopt as standards. Some of the participants are pursuing standardization of these components under the auspices of HL7.

Decision Support Systems, Clinical↗