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Ash Ketchum talks to Gary about Molecule 58 only to find out some new information!

After finally realizing how big of a mistake it was to let Molecule 58 get away, he talked with Gary about his encounter. Ash used Gary's story as evidence for his when he went to visit the other trainers, just like we used reference articles to support our reaction.

Original Article: Wang, Z. -G.; Warren, J. D.; Dudkin, V. Y.; Zhang, X.; Iserloh, U.; Visser, M.; Eckhardt, M.; Seeberger, P. H.; Danishefsky, S. J. Tetrahedron 2006, 62, 4954-4978.
Reference from the paper that we are using:

1. Weinreb, S. M.; Demko, D. M.; Lessen, T. A.; Demers, J.P. Tetrahedron Lett. 1986, 27, 2099-2012.

A.  Sulfonamides are one of the most stable of amine protecting groups. However, it is this stability that keeps them from being utilized as often, since extreme conditions are usually needed for their removal. The synthesis of a sulfonamide protecting group 1 can be readily cleaved by a fluoride ion to regenerate the “parent amine” as shown in eq. 1.  These sulfonamides can be readily prepared from a primary or secondary amine and trimethylsilylethanesulfonyl chloride (3), which is abbreviated SES-Cl. SES-Cl is a stable, distillable liquid that can be stored indoors for weeks at room temperature. It can also be purified by chromatography on silica gel. Sulfonamides can be prepared from a wide variety of primary and secondary amines using sulfonyl chloride (3) in DMF-containing  triethyl amine. In summary, SES-Cl allows formation of sulfonamides in a high yield.  SES-Cl are quite stable and can be removed with fluoride ions under conditions compatible with a variety of functional groups. This is why sulfonamides are awesome!

B. Jolicoeur, B.; Chapman, E. E.; Thompson, A.; Lubell, W. D. Tetrahedron 2006, 62, 11531-11563.
The N-trimethylsilylethanesulfonyl (SES) group was developed for pyrrole protection because it can be removed under mild conditions using tetrabutylammonium fluoride (TBAF) in THF at room temperature.  This is similar to our mechanism in which we are protecting the amine.

C.  Chambert, S.; Desire, J.; Décout, J.L. Synthesis 2002, 16, 2319–2334.
The 2-(trimethylsilyl)ethanesulfonamido group has been used for protection of amine functions leading to silyl sulfonamides (Scheme 38 shown in the attached page.)  Again, this is an article portraying the effectiveness of the protecting group on an amine.

D.  Hoye, R. C.; Richman, J. E.; Dantas, G. A.; Lightbourne, M. F.; Shinneman, L. S. J. Org. Chem. 2001, 66, 2722–2725.
The SES group was predicted in this article to have the same role as a tosyl group: protection of other secondary nitrogen atoms that are present in the polyamine substrate. A potential advantage of using the SES protecting group is that the SES-sulfonamide can be easily cleaved under mild conditions to generate the parent amine with cesium fluoride in DMF.  Our article uses the same conditions and reagents to remove the protecting group to form the lactosamine donor.

1. Danishefsky, S. J.; Gervay, J.; Peterson, J. M.; McDonald, F. E.; Koseki, K.; Oriyama, T.; Griffith, D. A.; Wong, C. -H.; Dumas, D. P. J. Am. Chem. Soc. 1992, 114, 8329-8331.

NOTE: We did not have 3 references to begin with.  We only had two.

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