Linked Life Data

21383141

Source:http://linkedlifedata.com/resource/pubmed/id/21383141

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2011-4-27
pubmed:abstractText
Complexity and the presence of stereogenic centers have been correlated with success as compounds transition from discovery through the clinic. Here we describe the synthesis of a library of pyran-containing macrocycles with a high degree of structural complexity and up to five stereogenic centers. A key feature of the design strategy was to use a modular synthetic route with three fragments that can be readily interchanged or "shuffled" to produce subtly different variants with distinct molecular shapes. A total of 352 macrocycles were synthesized ranging in size from 14- to 16-membered rings. In order to facilitate the generation of stereostructure-activity relationships, the complete matrix of stereoisomers was prepared for each macrocycle. Solid-phase assisted parallel solution-phase techniques were employed to allow for rapid analogue generation. An intramolecular nitrile-activated nucleophilic aromatic substitution reaction was used for the key macrocyclization step.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6751-6
pubmed:dateRevised
2011-10-26
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Fragment-based domain shuffling approach for the synthesis of pyran-based macrocycles.
pubmed:affiliation
Chemical Biology Platform, Broad Institute, Cambridge, MA 02142, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural