tag:blogger.com,1999:blog-8964719845369935777.post7489719884576138017..comments2024-03-27T21:23:40.339-04:00Comments on Chemjobber: Process Wednesday: the headaches of low yieldsChemjobberhttp://www.blogger.com/profile/15932113680515602275noreply@blogger.comBlogger5125tag:blogger.com,1999:blog-8964719845369935777.post-44383052149216070822012-10-17T20:04:07.851-04:002012-10-17T20:04:07.851-04:00True, while we strive for an "excellent"...True, while we strive for an "excellent" yield, I am happy to take a 60% yield in a step that has been optimized for both reaction and purification, if that one step of chemistry eliminates three steps at 90% yield. Its worth considering, as all the time and expense to manufacture those steps adds up to sometimes more in cost than the lower 60% yielding reaction does. It depends on the project, that is, the demand, the dose, and how well the purification of the 60% step is. These things need to be looked at in the full context of a project. And every project is different.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-8964719845369935777.post-17734452246802856042012-10-17T12:40:48.765-04:002012-10-17T12:40:48.765-04:00I don't have access to full article but the st...I don't have access to full article but the statement in the Abstract "if it can be measured, then it can be managed" as guiding principle smacks directly of MBA/Six Sigma meme. I trust the actual paper does not get bogged down by such mantra which recognize can have a place in "D" and certainly can benefit Manufacturing but applications to "R" can often be more inhibitory than helpful since it is difficult to place strict metrics on things in constant flux.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-8964719845369935777.post-71500450355032870152012-10-17T12:32:19.684-04:002012-10-17T12:32:19.684-04:00Digressing a bit and returning to that natural pro...Digressing a bit and returning to that natural product and genotoxic and other toxic impurities. Our clever pharma development had an in silico tox. department. Now the synthesis was 35 steps long and they insisted we carry out this aforementioned evaluation. That's OK with me but not for the entire 35 steps! It would have been reasonable for the GMP part. Not surprisingly 90% of the intermediates were negative, because they were all protected with silyl groups.<br />QA received a copy of the report. Of course there were reagents at the start and within the first third of the synthesis which were/are toxic in one form or another. I was asked "prove to us that these products are not in the drug substance." A HUGE argument ensued (which we eventually won) saying that after 25 steps and innumerable chromatography's and crystallisations that they were extremely unlikely to be present. To satisfy the QA people I had to sign a statement to that cause. Idiots they were, idiots.<br />It would have meant, had I not got my way, developing analytical methods for each reagent utilised in the synthesis. Idiots they were, idiots.<br />Anonymoushttps://www.blogger.com/profile/15287977920784124907noreply@blogger.comtag:blogger.com,1999:blog-8964719845369935777.post-79568843440090316562012-10-17T12:13:28.872-04:002012-10-17T12:13:28.872-04:00When I worked on the natural product development w...When I worked on the natural product development we examined the literature in great detail. The quoted yields ranged from 8% to 35% overall for synthesis of 40 steps or more. <br />A good question to ask at meetings when someone quotes yields of 60% is to ask "what is the other 40%?".<br />Another is to comment/ask "if your yields vary between 30%-80% (and such are quoted) then you do not have your reaction under control, why do the yields vary so much?"Anonymoushttps://www.blogger.com/profile/15287977920784124907noreply@blogger.comtag:blogger.com,1999:blog-8964719845369935777.post-46654441646993187022012-10-17T11:43:42.012-04:002012-10-17T11:43:42.012-04:00FYI
http://science.slashdot.org/story/12/10/16/19...FYI<br /><br />http://science.slashdot.org/story/12/10/16/1938246/faculty-to-grad-students-go-work-80-hour-weeksAnonymousnoreply@blogger.com