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Combinatorial & Parallel Synthesis

by: Evan Roberts

Combinatorial & Parallel Synthesis CH 405/505

Marketplace > University of Alabama - Tuscaloosa > Chemistry > CH 405/505 > Combinatorial Parallel Synthesis
Evan Roberts
GPA 3.57
Medicinal Chemistry
Timothy Snowden

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About this Document

These notes/handouts describe the strategies and techniques of combinatorial and parallel synthesis, and the pros/cons of each. Identification strategies for isolating a lead from a "mix & split" c...
Medicinal Chemistry
Timothy Snowden
Class Notes
25 ?




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This 20 page Class Notes was uploaded by Evan Roberts on Friday February 27, 2015. The Class Notes belongs to CH 405/505 at University of Alabama - Tuscaloosa taught by Timothy Snowden in Spring2015. Since its upload, it has received 108 views. For similar materials see Medicinal Chemistry in Chemistry at University of Alabama - Tuscaloosa.

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Date Created: 02/27/15
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Melwwemwr 0L Swath9341111 each Carj ounoIM39V UWU7 g p 05 ve regulL 39 9 umduiackn39 Combivtdac39wA Shruchzre Hm bul iun POOL H V gt r P du 3 C5 FeCuJ BdLL deconvolukm u mamma sgsu m Jahl fr jlek 3 4 warm he CLclwz comPou ad ma as 4392 133 21 Recursive deemnwo lu om oMethod of identifying the active component in a mixture Quicker than separately synthesizing all possible components Need to retain samples b eforeiggchgmix and split stage Emmple Consider all 27 tripeptides synthesized by the mix and split strategy from glycine alanine and valine 0 GL ampGly 0 ap 0 0 Jim s Mix and Split J2 gmn 1 Gly 1 Ala GEGIy Gly to iGly Aln 1 a O Aln Gly Q AIn Mn Ia i aI Gly min M All possible dipeptides in three vessels Retain a sample from each vessel and label by compound just added O Glya lg o Ala Gly O W 1 Gly o GIy Alu o Alu Alu o L t I 0 Gly L o Alal 39l I o l Mix and Split 0 Gly Gly O AIu Gly O a GI 0 GIy mn O Am Mn 0 0 3 a In o Gly Gly Q Mn Gly ou EHGy J GEGly Alu o Alu Aln a An 0 Gly I o Gly 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dipeptide mixtures Mixture Active 39ir onvoln on 21 Rmmrsive 39OGlly Glynwiml I gamm Gly n Q Alu Mn a a J 7 I0 ili iJu n i i Gly i 13 VII AIquotI m a iii Active Requires additional screening but active component narrowed down to one of three possible trip39eptides Synthesize each tripeptide and test 2 Identi cation of sh oUse a coding or encryption method employing a triplet code Three tags AC can be used to represent up to seven reagents for the rst stage of a synthesis 49 from combinatorial synthesis Reagent Tagging molecule 1 A B C AB AC BC ABC qamamu Identi cation of from synthesis Three different tags DF can be used for up to seven reagents used in the second stage of the synthesis Tags DF are chosen to have a Ivon gfenletengollime on a gas chromatograph com ared to tags AC 39 L z I p L Lm PQYi hri 40 furKt I ageigmmj 2 co m u39uTutohck Reagent Tagging molecule 91an3 33 mg a 3 a Lia0 1 D S fmiwergyl on 2115 E F DE DF EF 39 DEF IGUIBUJN lden ea o of slimetug Ear ending from combinatorial synthesis Tags are linked to bead by a photocleavable bond Irradiation removes all the tags at the same time Mixture is passed through a gas chromatograph quot1 r 1 59 quotTr if 43quot 5quot HM S fW l W306 u Tags are identified by their retention time 1 mg in Fla Vt 39 39 E 391 39Erl n39 fa 1mm quot 7 gt7 uquotquot Mar I MEL I w39 i If r I 7 3quot59 15 We Ligr i w WW if m m r v V t 7 7 E or 7 frim a r F39 e 5 oAbsence or presence of tags Identi es reagents used at di erent stages of the quot 39 quot 2 M39 2 gm lamb star a lifltnw synthesns a I 1quot h 39u39wf r h m iz 39 i Identifies the product assuming reaction goes as predicted L 615k Snowman quotnow Wg Cg ice uric O Sunk I ma 0v 6 Frog 7 Ftorq cm lQ tf39b in 31 ii a n r I 4 mullme QM i x 9mm wamw b E a gi Q Vania 553 61 f a i D I ESP as o f n 2 Identi cation of 22 v Gas chromatogram Retention i i 7 l time 1 O 1 l 1 Barcode Y T l L Y 1 lst reagent 2nd reagent 3rd reagent A B C D E F G H l Molecularja 0 l l jquot F lrra 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