September 30, 2022, 03:07:55 AM
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Topic: Schmidt glycosylation problems  (Read 3412 times)

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Offline Babcock_Hall

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Re: Schmidt glycosylation problems
« Reply #30 on: June 17, 2022, 10:59:14 AM »
We have been trying to follow literature models, including the order of addition, as closely as possible.  However we did communicate with a carbohydrate chemist yesterday who suggested adding TMSOTf before adding the alcohol as an option.  There are a great number of variables to explore.

Offline rolnor

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Re: Schmidt glycosylation problems
« Reply #31 on: June 18, 2022, 12:42:04 AM »
Sounds good.

Offline Babcock_Hall

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Re: Schmidt glycosylation problems
« Reply #32 on: June 29, 2022, 01:22:52 PM »
You can mix the protected methylglucopyranoside with TMSBr to get the bromo-sugar and then react this with the alcohol+1,1eqv. TEA in DCM.
This is starting to look more attractive, but I have not searched it via SciFinder yet.  One can buy tetra acetyl 1-bromoglycosides, and I found one supplier that is particularly inexpensive.
« Last Edit: June 29, 2022, 01:59:04 PM by Babcock_Hall »

Offline rolnor

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Re: Schmidt glycosylation problems
« Reply #33 on: June 29, 2022, 03:41:04 PM »
That sounds great if you can buy the bromosugar. Its like putting on a MEM-group on a alcohol.
It can be a bit slow because you have bulk but it should be OK. I know people use additives such as silver perchlorate. I think TEA makes a triethylammonium species with MEM-chloride so its a catalyst. Silver triflate could be very effective also for speeding things up. Solvent acetonitrile I think.

Offline Babcock_Hall

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Re: Schmidt glycosylation problems
« Reply #34 on: June 29, 2022, 08:17:56 PM »
Rituparna Das and Balaram Mukhopadhyay "Chemical O-Glycosylations: An Overview," ChemistryOpen 2016, 5:401–433.  DOI:10.1002/open.201600043
This is a good review at moderate depth.

Offline rolnor

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Re: Schmidt glycosylation problems
« Reply #35 on: June 30, 2022, 06:55:32 AM »
I had 3,5-O-p-Toluylribofuranosyl chloride and dissolved this in MeOH+TEA, I got a very nice yield of the 1-O-Methyl ribofunanoside. The bromosugar is more reactive than chloro.

Offline Babcock_Hall

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Re: Schmidt glycosylation problems
« Reply #36 on: August 30, 2022, 05:06:00 PM »
We are trying to couple a donor (tetra-acetylglucose-trichloromethylimidate) to an alcohol acceptor.  The other functional groups on the alcohol are a sulfonyl group and a diethyl ester of a phosphonate.  We used BF3-etherate as the acid promoter.  The purified product had H-1 NMR signals for both portions of the molecule, although the integrals for the glucose portion were a little lower than theoretical.  Unfortunately the yield was in the vicinity of 10%.  In my reading boron trifluoride and TMSOTf are the most commonly used Lewis acid promoters.  I might be inclined to look for an alternative Lewis acid, but realistically we are running out of time.

Offline rolnor

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Re: Schmidt glycosylation problems
« Reply #37 on: September 01, 2022, 01:56:34 AM »
Thats sad to hear, you need time to fix this. Or luck…
To make a new invention , like finding another, more suitable Lewis-acid, is a long-term project, not a quick-fix.
Try the glycosyl-bromide+the alcohol.

Offline Babcock_Hall

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Re: Schmidt glycosylation problems
« Reply #38 on: September 02, 2022, 05:43:27 PM »
Is there something in particular about the brominated derivative that you think makes it a good choice?

Offline rolnor

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Re: Schmidt glycosylation problems
« Reply #39 on: September 03, 2022, 06:36:54 AM »
Chloride is also fine.

Offline Babcock_Hall

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Re: Schmidt glycosylation problems
« Reply #40 on: September 03, 2022, 09:38:02 AM »
Why are either the chloride or bromide preferable to the trichloromethylimidate? 

Offline rolnor

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Re: Schmidt glycosylation problems
« Reply #41 on: September 04, 2022, 10:20:16 AM »
You dont need Lewis acid for the halides.

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