Comments on: Vindoline

By: TotallySynthetic.com » Blog Archive » Fendleridine

TotallySynthetic.com » Blog Archive » Fendleridine — Mon, 15 Feb 2010 22:08:34 +0000

[...] blogged papers back-to-back from one group! This target has clearly developed from their work in vindoline and vinblastine, using similar synthetic techniques. Their interest in this target in particular [...]

By: Finally…Total Synthesis:NOS Day 4 at C&ENtral Science

Finally…Total Synthesis:NOS Day 4 at C&ENtral Science — Fri, 12 Jun 2009 18:29:50 +0000

[...] and Phil Baran took the stage. Boger described what his group has learned over the years about vinblastine, a natural product that he quipped “needs no introduction”. (Just to be polite, [...]

By: Vinblastine at TotallySynthetic.com

Vinblastine at TotallySynthetic.com — Mon, 15 Oct 2007 22:23:08 +0000

[...] no synthesis of that here. However, those of you with good memories will remember we covered Boger’s synthesis of that nugget last [...]

By: Hap

Hap — Wed, 26 Jul 2006 22:51:24 +0000

The diazo compounds don’t need 180C, but even if they did they probably wouldn’t be able to stand it. The thermal conditions aren’t great, but the compound should be bench-stable (and unreactive under most conditions); it also doesn’t have a whole lot of complexity, and any complexity present can be assembled piecewise. The rhodium catalyst for diazo compound cycloaddition runs about $160/g (Aldrich, ’03 – probably about $20 for a 5 mmol-scale reaction), and the diazo compound is going to have to be generated from something else more stable. Unless the reaction is messy and has lots of byproducts, thermal (that doesn’t require FVP or any of its ilk) reaction of a stable precursor seems preferable to the generation of a diazo compound followed by RT reaction – but YMMV.

By: TPG

TPG — Wed, 26 Jul 2006 19:44:46 +0000

No, that’s why I said reagent or catalyst. I was speaking more in general terms, though I’ve worked with many substrates with a variety of sensitive functionalities that would tolerate 180 for up to 48 h with little protest. If you have other functionalities present that could be affected by a certain catalyst, thermal conditions may be preferable. The lower the catalyst loading, the less chance of undesirable side reactions, I agree, however.

By: Tot. Syn.

Tot. Syn. — Wed, 26 Jul 2006 18:16:46 +0000

The Org Lett in question:
http://dx.doi.org/10.1021/ol051975x

By: ddd

ddd — Wed, 26 Jul 2006 17:57:55 +0000

To TPG: do you classify 1 mol% catalyst in the reaction mix as a “reagent”????? While yor temperature goes down from 180 to ambient…

By: TPG

TPG — Wed, 26 Jul 2006 17:52:36 +0000

My mistake, it was an Org Lett paper, 2005, 7, 4539.

By: TPG

TPG — Wed, 26 Jul 2006 17:11:12 +0000

I guess it depends on your perspective and the types of molecules you’re used to working with, but I would consider a reaction that calls for heat and no reagents to be milder and cleaner then one that calls for no or less heat and a reagent or catalyst. I think Boger published a JACS communication not too long ago on Vindoline. I think this is the followup full paper.

By: ddd

ddd — Wed, 26 Jul 2006 15:49:51 +0000

yep..and rhodium is more friendly and does not require 180…Carbonyl ylides. Actually Schreiber used exact Padwa’s strategy in a recent org lett paper something like “folding strategy in combinatorial…blah blah blah alkaloids”