tag:blogger.com,1999:blog-1136153439451224584.post8562388856076681465..comments2024-03-27T06:45:59.174-07:00Comments on Practical Fragments: Pointless stereochemistryDr. Teddy Zhttp://www.blogger.com/profile/07288045760981372367noreply@blogger.comBlogger3125tag:blogger.com,1999:blog-1136153439451224584.post-4790759772644208522018-02-08T21:12:17.276-08:002018-02-08T21:12:17.276-08:00Hi Paul,
You bring up good points, and in fact ac...Hi Paul,<br /><br />You bring up good points, and in fact according to our recent <br /><a href="http://practicalfragments.blogspot.com/2017/10/poll-results-does-your-primary-fragment.html" rel="nofollow">poll</a> almost everyone includes racemates in their libraries. That said, if you do get a racemic hit, testing the pure enantiomers individually can be a useful (though not absolute) indicator as to whether the hit is real or not. <br /><br />The issue the authors are concerned about is that even if you do find a chiral hit, it will rapidly racemize, so a stereoselective synthesis is not worthwhile. <br /><br />One potential solution would be to lock the stereocenter by replacing the hydrogen with, for example, a methyl group, though this may not be tolerated, and could also be synthetically challenging.Dan Erlansonhttps://www.blogger.com/profile/07927082337051189270noreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-52206934979575251262018-02-08T01:45:29.813-08:002018-02-08T01:45:29.813-08:00How much would these fragments have to alter to in...How much would these fragments have to alter to increase the half-life?Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-1136153439451224584.post-86078402828458316812018-02-06T18:49:50.849-08:002018-02-06T18:49:50.849-08:00I can't help feeling that most steroselective ...I can't help feeling that most steroselective synthesis for fragments is pointless. Chiral pool is fine, but the added effort of genuine steroselective synthesis is hard to justify. Back in the day, fragment libraries were often run as mixtures of 10 or so different compounds, remember? So I can't see the harm of having two enantiomers or even diasteriomers for that matter in the well. If the protein is really selective for one isomer (and that happens less often than you might think) it be sorted out later. The main criterion for screening is efficiency, and complex steroselective routes don't cut it in my view.Paul Savagenoreply@blogger.com