Late Stage Functionalization

Starters & Essentials FunctionalizationPurification Analysis

Functionalization
 

The Late Stage incorporation of small, non-fluorous alkyl groups like methyl and ethyl has remained an unmet challenge. With phenomena like the magic methyl effect becoming increasingly understood and utilized within Lead Optimization, methods that incorporate these functionalities effectively and chemoselectively have been the topic of great interest. Ultimately, a photocatalytic approach allows for just this: the incorporation of methyl, ethyl and cyclopropyl functionality directly to complex bioactive small molecules.

Photocatalysis

Products

Late Stage Alkylation

Product No. Description
L511765 [Ir{dF(CF3)ppy}2(dtbpy)]PF6
388076 Tert-Butyl peracetate solution, 50 wt. % in odorless mineral spirits

Visible Light Photocatalysts

Product No. Description
90819 Bis(2,2′-bipyridine)-(5-aminophenanthroline)ruthenium bis(hexafluorophosphate)
L511803 Cu(dap)2 chloride
658383 Dichlorotetrakis(2-(2-pyridinyl)phenyl)diiridium(III)
343714 Dichlorotris(1,10-phenanthroline)ruthenium(II) hydrate
L511765 [Ir{dF(CF3)ppy}2(dtbpy)]PF6
L511838 [Ir(dtbbpy)(ppy)2][PF6]
L511811 9-Mesityl-10-methylacridinium perchlorate
L511781 [Ru(bpm)3][Cl]2
L511773 [Ru(bpz)3][PF6]2
224758 Tris(2,2′-bipyridyl)dichlororuthenium(II) hexahydrate
688096 Tris[2-phenylpyridinato-C2,N]iridium(III)

 

Literature & Resources
 

Tech Spotlight: Photocatalysis
Read our Technology Spotlight on Photocatalysis to see how photocatalysis is being applied to address the latest problems in synthetic chemistry.
 
 
Aldrich Professor Portals
The Sigma-Aldrich Professor Portals display the latest developments (and commercialized products) stemming from our pipeline of academic collaborators. This includes innovation in photocatalysis by Profs. Molander, Yoon and Stephenson.

The Baran Diversinates™ enable Late Stage Functionalization of heteroaromatic C-H bonds without the need for chemical handles or pre-functionalization. With operational simplicity (reactions are not sensitive to air or moisture), this suite of reagents can impart a diverse range of new functionality to simple heterocycles and complex bioactive small molecules, alike. Indeed, a growing list of Baran Diversinates™ allows for the inclusion of both pharmaceutically relevant bioisosteres and new bioconjugation linkers to your lead compound.

Products

Diversification/Bioconjugation-Ready Pharma Developed Compounds

Alkyl Diversinates

Product No. Description
ALD00288 Sodium tert-butylsulfinate
ALD00290 Sodium 2,2-dimethylpropylsulfinate
ALD00294 Sodium ethylsulfinate
790796 Zinc benzylsulfinate
792187 Zinc bis[(phenylsulfonyl)methanesulfinate]
790788 Zinc chloroethanesulfinate
791105 Zinc chloromethanesulfinate
745480 Zinc isopropylsulfinate
791040 Zinc n-propylsulfinate

 

Fluorinated Alkyl Diversinates

Product No. Description
745405 Sodium 1,1-difluoroethanesulfinate
ALD00238 Sodium trifluoropropylsulfinate
767840 Zinc difluoromethanesulfinate
745499 Zinc trifluoroethanesulfinate
771406 Zinc trifluoromethanesulfinate


Heterocyclic Building Blocks

Cyclic Diversinates

Product No. Description
ALD00296 Sodium adamantylsulfinate
ALD00254 Sodium 4-N-Boc-piperidinylsulfinate
ALD00234 Sodium tetrahydrofuransulfinate
ALD00232 Sodium tetrahydropyransulfinate

 

Fluorinated Cyclic Diversinates

Product No. Description
ALD00230 Sodium 4,4-difluorocyclohexanesulfinate
790184 Sodium 1-(trifluoromethyl)cyclopropanesulfinate

 

Cyclic Diversinates

Product No. Description
458139 Luperox® TBH70X, tert-Butyl hydroperoxide solution, 70 wt. % in H2O

 

Bioconjugation Diversinates

Product No. Description
746118 Sodium difluoroheptylazidosulfinate
792446 Sodium 1,1-difluoro-4-(2-methyl-1,3-dioxolan-2-yl)butane-1-sulfinate

Literature & Resources
 

Sharpless Sulfonyl Fluorides allow for the rapid inclusion of building-block type moieties into Lead compounds. The "Click II" reaction is, like its Alkyne-Azide predecessor, fast and quantitative, with the sulfonyl fluoride group reacting predictably with nucleophiles on your Lead Compound, all the while remaining inert to oxidation, reduction, thermolysis and other reactive conditions.

ESF- Render Your Lead Compound Clickable!
Pendant functionalization of your Lead Compound can be achieved with the bimodal ESF reagent. Indeed, ESF acts as a Michael -acceptor to covalently link nitrogen, oxygen and carbon nucleophiles in your Lead to a pendant sulfonyl fluoride group, ripe for further functionalization and diversification.

Products

Bimodal Clickable Tether

Product No. Description
746959 Ethenesulfonyl fluoride

Sulfonyl Fluoride Functionalization Reagents

Product No. Description
ALD00044 2-Phenylethenesulfonyl fluoride
ALD00058 5-Bromo-2-methoxybenzenesulfonyl fluoride
ALD00064 2,5-Dimethoxybenzenesulfonyl fluoride
ALD00052 4-Chloro-3-nitrobenzenesulfonyl fluoride
ALD00056 2-Naphthalenesulfonyl fluoride
ALD00126 [1,1′-Biphenyl]-4-sulfonyl fluoride
ALD00192 2-Chlorobenzenesulfonyl fluoride

Literature & Resources
 

Professor Portal - Barry Sharpless
Learn more about the Sharpless Lab - bridging the gap from innovative research to commercially available synthetic tools.
 
Drug Discovery Workflow

Sigma-Aldrich's comprehensive offer in Drug Discovery, from Target ID & Validation, Lead Discovery & Optimization, through Pre-Clinical into commercial manufacture.

Incorporation of fluorine can positively affect the metabolism, delivery and activity of bioactive small molecules. For these reasons, fluorine is found in over 25% of currently approved FDA drugs, despite being present in a near-negligible portion of naturally occurring small molecules. Two avenues of fluorine incorporation are available to the medicinal chemist: the use of fluorinated building blocks in a de novo synthesis or the direct,  late stage functionalization of bioactive molecules. Solutions to affect the latter are found below.

Products

Fluorine Containing Baran Diversinates
Baran Diversinates allow for the operationally simple inclusion of fluoroalkyl functionality to both simple heterocyclic building blocks (early stage), and to complex heterocyclic small molecules (late stage) with remarkable selectivity.
 

Product No. Description
771406 Zinc trifluoromethanesulfinate
767840 Zinc difluoromethanesulfinate
745499 Zinc trifluoroethanesulfinate
745405 Sodium 1,1-difluoroethanesulfinate
ALD00238 Sodium trifluoropropylsulfinate
790184 Sodium 1-(trifluoromethyl)cyclopropanesulfinate
ALD00230 Sodium 4,4-difluorocyclohexanesulfinate
746118 Sodium difluoroheptylazidosulfinate
792446 Sodium 1,1-difluoro-4-(2-methyl-1,3-dioxolan-2-yl)butane-1-sulfinate

 

Classic Nucleophilic Fluorination Reagents

Product No. Description
235253 (Diethylamino)sulfur trifluoride
774642 (Diethylamino)sulfur trifluoride solution
494119 Deoxo-Fluor®
94327 Deoxo-Fluor® solution
94324 Deoxo-Fluor® solution
734039 4-tert-Butyl-2,6-dimethylphenylsulfur trifluoride
719447 XtalFluor-M®
719439 XtalFluor-E®

 

PhenoFluor: Unprecedented Deoxyfluorination
PhenoFluor affects the ipso-substitution of phenols and seconary alcohols with fluorine (a deoxyfluorination), reacting efficiently where other reagents such as DAST and XtalFluor are less effective.

Product No. Description
SFL00001 PhenoFluor™

 

Classic Electrophilic Fluorination Reagents

Product No. Description
439479 Selectfluor® fluorinating reagent
323659 1-Fluoropyridinium triflate
738123 2,6-Dichloro-1-fluoropyridinium triflate
392715 N-Fluorobenzenesulfonimide

Fluorination-Ready
Pharma Developed Compounds




Fluorinated Building Blocks


Fluorination
Visit the Sigma-Aldrich Fluorination Reagents page.





Download Fluorination Guide
Download our useful guide containing classic methods for the introduction of fluorine, difluoromethyl and trifluoromethyl functionality. A look at fluorinated building blocks is also provided.

Sigma-Aldrich offers bioconjugation reagents for cellular delivery of your optimized Lead Compound, including crosslinkers for conjugation to targeting biomolecules and PEGylation reagents for enhancing pharmacokinetics.  Our selection of crosslinkers and PEGylation reagents contain diverse functional groups, such as amines, maleimides, and azides.

Products

Featured Crosslinkers

Product No. Description
38263 21-(Boc-amino)-4,7,10,13,16,19-hexaoxaheneicosanoic acid
80424 Di(N-succinimidyl) glutarate
M6035 4-(N-Maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt
711632 N-Boc-iminodipropionic acid
14766 2-[2-(Boc-amino)ethoxy]ethoxyacetic acid (dicyclohexylammonium) salt
89761 N-Boc- 2,2′-(ethylenedioxy)diethylamine
A0638 Adipic acid dihydrazide
764167 Alkyne-PEG5-acid
764248 2-Acetyl-3-chlorothiophene

Peptide Chemistry

Antibodies


Featured Bioorthogonal Reagents

Product No. Description
764493 5-[4-(1,2,4,5-Tetrazin-3-yl)benzylamino]-5-oxopentanoic acid
764523 (E)-Cyclooct-4-enyl 2,5-dioxo-1-pyrrolidinyl carbonate
678937 Tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine
670359 Acetylthiomethyl-diphenylphosphine borane complex
762040 Dibenzocyclooctyne-sulfo-N-hydroxysuccinimidyl ester
765953 1,11-Diazido-3,6,9-trioxaundecane

 

Featured Pegylation Reagents

Product No. Description
712558 Methoxypolyethylene glycol maleimide
41214 O-[(N-Succinimidyl)succinyl-aminoethyl]-O′-methylpolyethylene glycol 2′000
743127 O-(2-Mercaptoethyl)-O′-methylpolyethylene glycol
726249 O-(2-Azidoethyl)nonadecaethylene glycol
07964 Methoxypolyethylene glycol amine
41964 O-[2-(6-Oxocaproylamino)ethyl]-O′-methylpolyethylene glycol 5′000
689777 O-[N-(3-Maleimidopropionyl)aminoethyl]-O′-[3-(N-succinimidyloxy)-3-oxopropyl]heptacosaethylene glycol
671592 O-(2-Aminoethyl)-O′-(2-carboxyethyl)polyethylene glycol 5,000 hydrochloride
712523 O-(3-Carboxypropyl)-O′-[2-(3-mercaptopropionylamino)ethyl]-polyethylene glycol

Literature & Resources
 

SAFC Manufacturing

Learn how SAFC® can develop and synthesize custom biomolecules and bioconjugates.
 
 
Click Chemistry Technical Spotlight
Click Chemistry has a variety of applications in drug discovery and bioconjugation - read our Click Chemistry Technical Spotlight to find out more.
Drug Discovery Workflow

Sigma-Aldrich’s comprehensive offer in Drug Discovery, from Target ID & Validation, Lead Discovery & Optimization, through Pre-Clinical into commercial manufacture.