Comments on: Isatisine A

By: ChemistryGuru

ChemistryGuru — Thu, 25 Feb 2010 07:02:27 +0000

I just wanted to digress for a moment to highlight a mistake in the discussion of the oxidation step. The supporting information notes the use of 2 equivalents of mCPBA. Of course, the initial equivalent is used for 2,3-epoxidation of the indole. However, the authors reference a paper by Kobayashi (Buller, M. J.; Cook, T. G.; Kobayashi, Y. Heterocycles 2007, 72, 163) as the logic for their mechanistic insight into the interesting oxidation transformation. That particular work hypothesizes that the mechanism of action following the indole nitrogen opening the epoxide is an Amadori rearrangement (relatively common to sugar chemistry) followed by N-oxidation. Elimination of water off of the protonated nitrogen at the 2 position reveals the electrophilic 2 position of the newly formed indolone, poised for intramolecular cyclization of the primary alcohol to give the 2,2-disubstituted indolone intermediate.

By: SomeGuy

SomeGuy — Sat, 13 Feb 2010 01:32:13 +0000

Word. I’ve certainly seen the same thing with radical changes in an eluent’s EtOAc content. Just for completeness’ sake and all.

By: Billy

Billy — Thu, 11 Feb 2010 11:18:25 +0000

I really don’t care what you do with you mother but there is no need for that language on a scientific blog which is gaining some repute as a place people can go and be educated. Please **** off!

By: chemist

chemist — Mon, 08 Feb 2010 20:29:38 +0000

Nice to see so many chemists here with interest in total synthesis.

Any idea whether total synthesis of FOSMIDOMYCIN (natural antibiotic) is reported. I could only find the synthesis of various analogues but not this drug.

Thanks

By: AIK

AIK — Wed, 13 Jan 2010 17:18:38 +0000

I’ve run DCM/MeOH/ammonia columns like a motherfucker and usually there’s no problem with silica going through but occassionally it has occurred.

By: milkshake

milkshake — Wed, 13 Jan 2010 10:18:16 +0000

silica actually does not dissolve in methanol – even when everybody (and his grandmother) swears it does. What happens instead is a strong exotherm from MeOH absorbing on the silica. You get a local hot zone at the methanol front that creates a turbulence and vapor pressure, this pushes the fine silica particulates through the sintered glass frit (or the cotton plug) on the bottom of your column so what comes out when the methanol front reaches the bottom of your column is gonna be cloudy.

If you do not use methanol in gradient gradient and if you pack your column as a slurry with the actual solvent mix used for elution you will not have problem with silica getting through regardless of the used methanol concentration

By: aaaa

aaaa — Wed, 13 Jan 2010 07:37:37 +0000

If you do not know the structure – sure you do not want to use something reactive to isolate the compound, but if you know – why not. We use in our company on daily basis – silica columns with added ammonia, acetic acid, acetone/water mixtures etc. No problem whatsoever, just think a bit before flashing. Also the BS about not using MeOH on silica – remember in my former lab people were arguing that more than 25% MeOH in the eluent dissolves silica. Yeah, books write about it. So, we took a column, filled with silica and eluted with pure MeOH in a 1L RBF. Evaporated – there was absolutely nothing! I personally have used pure MeOH with 10% added aqueous conc. ammonia on silica without any problems at all. Thinking back I clearly see that academia people have actually many myths going around in the labs, because the lab experience in a normal academi lab is no longer than 4-5 years, then people just leave. And a cler lack of industrial experience is the missing point in academic research, as I see it now.

By: MSG

MSG — Tue, 12 Jan 2010 23:17:07 +0000

Just to clarify: I guess what i’m questioning is the use of acetone/silica when isolating natural products. In these cases you cannot be completely sure what sort of compounds you have in the mixture, and even if you know you don’t have alcohols in there, aldol adducts are also possible. Ethyl acetate is much more inert than acetone in regards to these possible reactions.

By: Tok

Tok — Tue, 12 Jan 2010 15:05:02 +0000

What’s wrong with acetone and silica? I’ve used hex:acetone to run dozens (hundreds?) of columns and have had no problems. As long as you don’t have a 1,2 diol or unprotected primary or secondary amine you should be fine. It’s actually quite nice in automated columns because it doesn’t absorb at 210nm and since it’s more polar than ethyl acetate it has a wider range of applicability.

By: milkshake

milkshake — Tue, 12 Jan 2010 02:27:00 +0000

just ask former Corey group member who worked on synthesis “endogenous quabain-like isomeric compound” and observe them doing both-handed facepalm. That natural compound isolated from cow brains that was supposed to be an isomer of quabain with a misplaced one hydroxy group. After several years of educated guesses about its structure and several semisynthetic attempts starting from quabain (just imagine a molecule like quabain and then try to move the hydroxyls around on the steroid piece through selective protections and transformations) it has been recognized by the Japanes group who originally isolated this wonder that the mystery molecyle is indeed quabain complexed with boric acid that was most likely picked up from glassware during the isolation. How quabain got into those cows brains is stil unexplained – either the cows ate the plants or some postdoc wanted to make his Japanes boss happy and added a tip of spatula to the material…