combinatorial chemistry online: volume 13, issue 11, november 2011

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Combinatorial Chemistry Online Volume 13, Issue 11, November 2011 N.K. Terrett Ensemble Therapeutics Corp., Cambridge, MA 02139, USA 1. Current literature highlights 1.1. A library of rapamycin analogues that bind to FKBP12 FK506 (1) and rapamycin (2) are natural products from micro- organisms that are effective immunosuppressant drugs. The tar- gets for FK506 and rapamycin are calcineurin and the ‘mammalian target of rapamycin’ (mTOR) respectively, but significantly their efficacy in binding originates firstly in their ability to modify the surface of FK506-binding protein 12 (FKBP12). It is the binary com- plexes of FK506 and rapamycin with FKBP12 that creates function- ality that can bind to the target proteins. Thus FK506 and rapamycin can be considered bifunctional molecules that have one molecular section that can bind to FKBP12, while the other, ‘effector’ domain binds to the target protein with evolved specific- ity. This property is remarkable as these are examples of molecules that can facilitate protein–protein interactions by modifying one protein surface and in doing so, make it readily recognised by a second protein. O Me HO O O N O O O MeO OH OMe Me OH H Me OMe 1 O O N O O O MeO OH Me OH H Me OMe Me H O Me Me HO Me OMe Me O 2 O O N O O O MeO OH Me OH H Me OMe Me H O Me Me HO Me OMe Me O 2 The goal of a recent publication was the design and synthesis of a number of rapamycin analogues that contained a common FKBP12 binding domain, but that also contained different effector domains so that in conjunction with the FKBP12 surface, they could generate a diverse range of composite surfaces that could be optimised for a target partner protein. 1 The common FKBP-binding moiety is a triketo pipecolyl core section of the macrocycles, and it was intended that this part of the combinatorial library would be invariant while the remainder of the compound was a variable peptide that had the potential to act as the effector region. To identify a reason- able, minimal FKBP-12 binding region, 15 cyclic peptides were constructed containing 10 different R 1 groups and three R 2 groups. A constant glutamine residue was included on the C- terminal side of the R 1 residue as the tether point for solid phase synthesis. Finally, Ala-Ala was another invariant part of the effector domain of the macrocycles. The 15 compounds were prepared in parallel on Rink amide resin, and after cleav- age from the solid support were testing for binding to FKBP12 in a fluorescence polarisation competition assay. The results indicated a preference for a D-b-homoPhe in the R 1 position, and D-Ala in the R 2 position, resulting in the tetrapeptide, D- Ala-Dkb-Pip-D-b-homoPhe as the constant FKBP12 binding domain. doi:10.1016/j.comche.2011.10.001 E-mail: [email protected] Combinatorial Chemistry - An Online Journal 13 (2011) 41–44 Contents lists available at SciVerse ScienceDirect Combinatorial Chemistry - An Online Journal journal homepage: www.elsevier.com/locate/comche

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Page 1: Combinatorial Chemistry Online: Volume 13, Issue 11, November 2011

Combinatorial Chemistry - An Online Journal 13 (2011) 41–44

Contents lists available at SciVerse ScienceDirect

Combinatorial Chemistry - An Online Journal

journal homepage: www.elsevier .com/locate /comche

Combinatorial Chemistry Online

Volume 13, Issue 11, November 2011N.K. TerrettEnsemble Therapeutics Corp., Cambridge, MA 02139, USA

1. Current literature highlights

1.1. A library of rapamycin analogues that bind to FKBP12

FK506 (1) and rapamycin (2) are natural products from micro-organisms that are effective immunosuppressant drugs. The tar-gets for FK506 and rapamycin are calcineurin and the ‘mammaliantarget of rapamycin’ (mTOR) respectively, but significantly theirefficacy in binding originates firstly in their ability to modify thesurface of FK506-binding protein 12 (FKBP12). It is the binary com-plexes of FK506 and rapamycin with FKBP12 that creates function-ality that can bind to the target proteins. Thus FK506 andrapamycin can be considered bifunctional molecules that haveone molecular section that can bind to FKBP12, while the other,‘effector’ domain binds to the target protein with evolved specific-ity. This property is remarkable as these are examples of moleculesthat can facilitate protein–protein interactions by modifying oneprotein surface and in doing so, make it readily recognised by asecond protein.

OMe

HO

O

O

NO

O

O

MeOOH

OMe Me

OH

HMe

OMe

1

doi:10.1016/j.comche.2011.10.001

E-mail: [email protected]

O

O

NO

O

O

MeOOH

Me

OH

HMe

OMe

MeH

O

Me

MeHO

Me

OMe

MeO

2

O

O

NO

O

O

MeOOH

Me

OH

HMe

OMe

MeH

O

Me

MeHO

Me

OMe

MeO

2

The goal of a recent publication was the design and synthesis ofa number of rapamycin analogues that contained a commonFKBP12 binding domain, but that also contained different effectordomains so that in conjunction with the FKBP12 surface, theycould generate a diverse range of composite surfaces that couldbe optimised for a target partner protein.1

The common FKBP-binding moiety is a triketo pipecolyl coresection of the macrocycles, and it was intended that this partof the combinatorial library would be invariant while theremainder of the compound was a variable peptide that hadthe potential to act as the effector region. To identify a reason-able, minimal FKBP-12 binding region, 15 cyclic peptides wereconstructed containing 10 different R1 groups and three R2

groups. A constant glutamine residue was included on the C-terminal side of the R1 residue as the tether point for solidphase synthesis. Finally, Ala-Ala was another invariant part ofthe effector domain of the macrocycles. The 15 compoundswere prepared in parallel on Rink amide resin, and after cleav-age from the solid support were testing for binding to FKBP12in a fluorescence polarisation competition assay. The resultsindicated a preference for a D-b-homoPhe in the R1 position,and D-Ala in the R2 position, resulting in the tetrapeptide, D-Ala-Dkb-Pip-D-b-homoPhe as the constant FKBP12 bindingdomain.

Page 2: Combinatorial Chemistry Online: Volume 13, Issue 11, November 2011

42 N.K. Terrett / Combinatorial Chemistry - An Online Journal 13 (2011) 41–44

NH

O

NH

N

OO

O

Ph

NH

O

O

HN

R4

O

R3 O

NHO

CONH2

3

NH

O

NH

N

OO

O

Ph

NH

O

O

HN R4

O

R3 O

HN

4

HN

O

O

CONH2

A library of 200 rapalog compounds was prepared on Rink amide re-sin in parallel. Half of the library (3) contained a diverse R3–R4

dipeptide sequence, while the other 100 compounds (4) employeda tripeptide R3–R4–L-Ala in the effector domain. Ten amino acidswere used in each of the R3 and R4 positions. The compounds wereindividually assayed for binding to FKBP12 by a fluorescence anisot-ropy competition assay and IC50 values determined. The majority ofcompounds had excellent to respectable affinities (IC50 = 2–93 lM),some of them only some 10-fold less potent than FK506. The libraryoffers the possibility of screening rapalog-FKBP composite surfacesfor their potential to inhibit currently intractable protein–proteininteractions.

2. A summary of the papers in this month’s issue

2.1. Solid-phase synthesis

No papers this month.

2.2. Solution-phase synthesis

A procedure for benzylic Suzuki–Miyaura cross-coupling undermicrowave conditions has been developed. The conditions allowedfor heterocyclic compounds to be coupled, with optimum condi-tions found to be Pd(OAc)2, JohnPhos as the catalyst and ligand,potassium carbonate as the base, and DMF as the solvent. Usingthese conditions, a library of structurally diverse compounds hasbeen synthesised.2

A facile diversity oriented synthesis of a- and b-amino acids, hasbeen described, using the a-methylene group in a chiral bicycliclactam as the key point of transformation. Conditions are currentlybeing optimised for an effective conversion of the a-amino acid sur-rogates to the final derivatives without a decrease in chiral purity.3

The parallel synthesis of a library of N1- and C3-substituted-pyrazolo[3,4-d]pyrimidines has been described. The microwave-

assisted approach involves the de novo generation of the heterocy-clic scaffold, facile alkylation at N1 via either a Mitsunobu or a di-rect alkylation reaction and arylation at C3 via a Suzuki reaction.4

2.3. Scaffolds and synthons for combinatorial libraries

A series of novel 3-benzhydryl-4-piperidone derivatives havebeen identified as potent tachykinin neurokinin-1 (NK1) receptorantagonists. An efficient and versatile synthesis of this series wasachieved with a coupling reaction of 1-benzylpiperidones withbenzhydryl bromides or benzhydrols in the presence of trif-luoromethanesulphonate and a condensation reaction of piperi-dones with benzyl alcohols. The 3-benzhydryl-4-piperidonescaffold, which has a 1,1-diphenylmethane moiety that is a knownprivileged substructure targeting G-protein coupled receptors, canbe used for chemical library synthesis because of its chemicalaccessibility and diversity.5

2.4. Solid-phase supported reagents

An improved method for the thionation of amides using a solid-supported P2S5 reagent has been described. Heating amides undermicrowave irradiation furnished thioamides in good to excellentyields, with a significantly reduced reaction time compared withthat achieved under conventional heating.6

Novel, efficient, and recyclable bifunctional catalysts bearingSiO2-supported RuCl3 and iodoarene moieties have been developedand used for environmentally benign oxidation of alcohols oralkylarenes at the benzylic position. These reactions in the pres-ence of oxone as stoichiometric oxidant gave the correspondingcarbonyl compounds in high yields under mild conditions and con-venient work-up. Furthermore, these SiO2-supported bifunctionalcatalysts can be recovered by simple filtration and directly reused.7

A thermally stable polymer-supported oxidant has been devel-oped. Polymer-supported 2-benzenesulphonyl-3-(4-nitro-phenyl)oxaziridine was applied to microwave-assisted reactionsthat occurred at high temperatures and was shown to oxidise al-kenes, silyl enol ethers, and pyridines to the corresponding epox-ides and pyridine N-oxides in excellent to good yields and withmuch shorter reaction times.8

2.5. Novel resins,linkers and techniques

Use of solid-phase synthesis for the derivatisation of carboxylicacids with biotinylated spacers consisting of ethylenoxy units hasbeen described. An aminomethylated resin containing an acid-la-bile aldehyde linker is used as the polymer support and three dif-ferent systems with a reactive amino group have been introduced.Acylation of each system was tested with a set of model carboxylicacids and afforded crude products of excellent purity. These proto-cols represent a very efficient way of modifying compounds to ob-tain ligands for affinity chromatography studies.9

2.6. Library applications

A diverse library of N,N-dimethylamino containing monomershas been reported. Subjecting these monomers to Chabrier reac-tion conditions yields lipids with polymerisable head groups. Thislibrary of lipid head groups is equipped with arms of variouslengths containing reduction–oxidation polymerisable groups atthe terminus.10

Three novel inosine-based dinuclear platinum complexes havebeen synthesised via a solid-phase strategy. These compounds con-tain the metal linked both to the N–7 of the purine nucleus and tothe terminal amine group of a hexylamine side chain installed onN–1. Cis- or trans-diamine as well as ethylenediamine ligands are

Page 3: Combinatorial Chemistry Online: Volume 13, Issue 11, November 2011

N.K. Terrett / Combinatorial Chemistry - An Online Journal 13 (2011) 41–44 43

coordinated to platinum along with a chloride. The synthesisedcomplexes were tested against four different human tumour celllines, and one of these complexes proved to be more cytotoxic thancisplatin against the MCF7 cancer cell line in a short-term exposureassay.11

RNA-peptide conjugates that mimic amino acid-charged tRNAsand peptidyl-tRNAs are of high importance for structural and func-tional investigations of ribosomal complexes. The synthesis of gly-cyl-, alanyl-, and isoleucyladenosine modified solid supports thatare eligible for the synthesis of stable 30-aminoacyl- and 30-pepti-dyl-tRNA termini with an amide instead of the natural ester link-age have been described. The present work significantly expandsthe range of accessible peptidyl-tRNA mimics for ribosomalstudies.12

The direct anti-tubercular testing of a small compound libraryhas led to the discovery of an adamantyl urea hit compound. Thehit was followed up through the synthesis of an optimisation li-brary, generated by systematically replacing each section of themolecule with a similar moiety until a clear structure–activity rela-tionship was obtained with respect to anti-tubercular activity. Thebest compounds in this series contained a 1-adamantyl-3-phenylurea core and had potent activity against Mycobacterium tuberculo-sis with an acceptable therapeutic index.13

Libraries of morpholines and oxazepanes have been preparedvia the reductive amination reaction between dialdehydes, derivedfrom carbohydrates, and a range of amines. The abilities of thesefunctionalised morpholines and oxazepanes to inhibit a broad pa-nel of glycosidase enzymes, that are associated with a range of dis-eases, have been probed and new inhibitors of a range ofglycosidases have been discovered.14

A family of norcantharidin analogues possessing a terminalalcohol (ethanol, propanol, butanol, pentanol, hexanol and cyclo-hexanol) moiety have been treated with either chlorodiethyl, chlo-rodiphenyl or chloro-bis-trichloroethyl-phosphate to afford highlyfocussed libraries of the corresponding phosphate esters. Subse-quent biological screening against a panel of nine human cancercell lines identified a trend between the ease of phosphateunmasking (phosphate ester hydrolysis) and cell death. The mostpotent analogues possessed either a diphenyl or a bis-trichloroeth-yl moiety.15

Most nucleosides in solution typically exist in equilibrium be-tween two major sugar pucker forms, N-type and S-type, butbridged nucleosides can be locked into one of these conformationsdepending on their specific structure. A recent study has investi-gated the potential for biological activity within these conforma-tionally-locked structures. A small library of 20,40- and 30,40-bridged nucleoside analogues was synthesised, and tested for anti-bacterial, antitumour, and antiviral activities, leading to the identi-fication of nucleosides possessing such biological activities.16

The cannabinoid receptor 2 (CB2) plays an important role in hu-man physiology and the pathophysiology of different diseases,including neuroinflammation, neurodegeneration, and cancer.The synthesis and results of in vitro receptor binding of a focusedlibrary of new fluorinated 2-oxoquinoline CB2 ligands has been re-ported. Twelve compounds were synthesised in good yields inmultiple steps. Preliminary in vitro results suggest that six of thesecompounds may be useful for therapy of neuropathic pain, neuro-inflammatory diseases and immune disorders.17

With an aim of developing novel protein tyrosine phosphatase(PTP) 1B inhibitors based on sugar scaffolds, a focused library ofbenzyl 6-triazolo(hydroxy)benzoic glucosides has been efficientlyconstructed via the modular and selective Cu(I)-catalysed azide-al-kyne 1,3-dipolar cycloaddtion (click chemistry). These glycoconju-gates bearing alkyl chain length-varied bridges between the sugarand (hydroxy)-benzoic moieties were identified as new PTP1Binhibitors with selectivity over T-Cell PTP (TCPTP), SH2-Containing

PTP-1 (SHP-1), SHP-2 and Leukocyte Antigen-Related TyrosinePhosphatase (LAR).18

Cathepsin B is a lysosomal cysteine protease that has variousphysiological and pathophysiological functions. The discovery of6-substituted 4-benzylthio-1,3,5-triazin-2(1H)-ones as inhibitorsof cathepsin B, starting from screening of a library of variously2,4,6-trisubstituted 1,3,5-triazines and 1,3,5-triazin-2(1H)-ones,has been described. The synthesis and enzymatic evaluation of afocused library of new 1,3,5-triazin-2(1H)-ones has also beendescribed.19

References

1. Wu X et al. Creating diverse target-binding surfaces on FKBP12: synthesis andevaluation of a rapamycin analogue library. ACS Comb Sci 2011;13(4):486–95.

2. McDaniel SW et al. Suzuki–Miyaura cross-coupling of benzylic bromides undermicrowave conditions. Tetrahedron Lett 2011;52(43):5656–8.

3. Sen S et al. Diversity-oriented synthesis of amino acids using chiral enolates.Tetrahedron Lett 2011;52(43):5585–8.

4. Todorovic N et al. Microwave-assisted synthesis of N1- and C3-substitutedpyrazolo3,4-dpyrimidines libraries. Tetrahedron Lett 2011;52(44):5761–3.

5. Shirai J et al. 3-Benzhydryl-4-piperidones as novel neurokinin-1 receptorantagonists and their efficient synthesis. Bioorg Med Chem 2011;19(17):5175–82.

6. Lagiakos HR et al. Thionation of amides using a solid-supported P2S5 reagentunder microwave irradiation. Tetrahedron Lett 2011;52(40):5131–2.

7. Zeng X-M et al. Recyclable silica-supported iodoarene–RuCl3 bifunctional cata-lysts for oxidation of alcohols and alkylarenes. Tetrahedron Lett2011;52(43):5652–5.

8. Susanto W, Lam Y. Oxidation reactions using polymer-supported 2-benzenesul-fonyl-3-(4-nitrophenyl)oxaziridine. Tetrahedron 2011;67(43):8353–9.

9. Cankarova N et al. Novel preloaded resins for solid-phase biotinylation ofcarboxylic acids. Tetrahedron Lett 2011;52(44):5782–8.

10. Jones IW et al. Synthesis of a diverse library of N,N-dimethylamino containingmonomers appropriate as lipid head groups. Tetrahedron Lett2011;52(43):5547–9.

11. D’Errico S et al. Solid-phase synthesis and pharmacological evaluation of novelnucleoside-tethered dinuclear platinum(II) complexes. Bioorg Med Chem Lett2011;21(19):5835–8.

12. Steger J, Micura R. Functionalized polystyrene supports for solid-phase synthesisof glycyl-, alanyl-, and isoleucyl-RNA conjugates as hydrolysis-resistant mimicsof peptidyl-tRNAs. Bioorg Med Chem 2011;19(17):5167–74.

13. Brown JR et al. The structure–activity relationship of urea derivatives as anti-tuberculosis agents. Bioorg Med Chem 2011;19(18):5585–95.

14. Burland PA et al. Synthesis and glycosidase inhibitory profiles of functionalisedmorpholines and oxazepanes. Bioorg Med Chem 2011;19(18):5679–92.

15. Robertson MJ et al. Norcantharimide analogues possessing terminal phosphateesters and their anti-cancer activity. Bioorg Med Chem 2011;19(18):5734–41.

16. Nicolaou KC et al. Synthesis and biological evaluation of 20 ,40- and 30 ,40-bridgednucleoside analogues. Bioorg Med Chem 2011;19(18):5648–69.

17. Turkman N et al. Fluorinated cannabinoid CB2 receptor ligands: Synthesis andin vitro binding characteristics of 2-oxoquinoline derivatives. Bioorg Med Chem2011;19(18):5698–707.

18. Li C et al. Click to a focused library of benzyl 6-triazolo(hydroxy)benzoicglucosides: novel construction of PTP1B inhibitors on a sugar scaold. Eur J MedChem 2011;46(9):4212–8.

19. Sosic I et al. Discovery and kinetic evaluation of 6-substituted 4-benzylthio-1,3,5-triazin-2(1H)-ones as inhibitors of cathepsin B. Eur J Med Chem2011;46(9):4648–56.

Further reading

Papers on combinatorial chemistry or solid-phase synthesis from other journals

Heinlein C, Silva DV, Troester A, Schmidt J, Gross A, Unverzagt C. Fragmentcondensation of C-terminal pseudoproline peptides without racemization onthe solid phase. Angewandte Chemie, International Edition 2011;50(28):6406–10.

Schaert D, Troiber C, Salcher EE, Froehlich T, Martin I, Badgujar N, et al. Solid-phasesynthesis of sequence-defined T-, i-, and U-shape polymers for pDNA and siRNADelivery. Angewandte Chemie, International Edition 2011;50(38):8986–9.

Joshi J, Mishra MK, Srinivasarao M. Silica-supported methanesulfonic acid - anefficient solid Bronsted acid catalyst for the Pechmann reaction in the presence ofhigher n-alkanes. Canadian Journal of Chemistry 2011;89(6):663–70.

Wu H, Ge J, Uttamchandani M, Yao SQ. Small molecule microarrays: the first decadeand beyond. Chemical Communications (Cambridge, England)2011;47(20):5664–70.

Vendrell M, Krishna GG, Ghosh KK, Zhai D, Lee J-S, Zhu Q, et al. Solid-phase synthesisof BODIPY dyes and development of an immunoglobulin fluorescent sensor.Chemical Communications (Cambridge, United Kingdom) 2011;47(29):8424–6.

Kodadek T. The rise, fall and reinvention of combinatorial chemistry. ChemicalCommunications (Cambridge, United Kingdom) 2011;47(35):9757–63.

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44 N.K. Terrett / Combinatorial Chemistry - An Online Journal 13 (2011) 41–44

Rodriguez-Docampo Z, Eugenieva-Ilieva E, Reyheller C, Belenguer AM, Kubik S, Otto S.Dynamic combinatorial development of a neutral synthetic receptor that bindssulfate with nanomolar affinity in aqueous solution. Chemical Communications(Cambridge, United Kingdom) 2011;47(35):9798.

Burchak ON, Mugherli L, Ostuni M, Lacapere JJ, Balakirev MY. Combinatorial discoveryof fluorescent pharmacophores by multicomponent reactions in droplet arrays.Journal of the American Chemical Society 2011;133(26):10058–61.

Sabatino D, Proulx C, Pohankova P, Ong H, Lubell WD. Structure-activity relationshipsof GHRP-6 azapeptide ligands of the CD36 scavenger receptor by solid-phasesubmonomer azapeptide synthesis. Journal of the American Chemical Society2011;133(32):12493–506.

Napolitano R, Soesbe TC, De Leon-Rodriguez LM, Sherry AD, Udugamasooriya DG. On-bead combinatorial synthesis and imaging of chemical exchange saturationtransfer magnetic resonance imaging agents to identify factors that influencewater exchange. Journal of the American Chemical Society 2011;133(33):13023–30.

Liu W, Chan ASH, Liu H, Cochrane SA, Vederas JC. Solid supported chemical synthesesof both components of the lantibiotic lacticin 3147. Journal of the AmericanChemical Society 2011;133(36):14216–9.

Chattopadhyay G, Ray PS. Hydrazine-hydroquinone complex as an efficient solidphase hydrazine donor: high yield synthesis of luminol and isoluminol. Journal ofChemical Research 2011;35(6):326–8.

Verhoest PR, Sawant Basak A, Parikh V, Hayward M, Kauman GW, Paradis V, et al.Design and discovery of a selective small molecule j opioid antagonist (2-methyl-N-((2’-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242). Journal of Medicinal Chemistry 2011;54(16):5868–77.

Sleebs MM, Scanlon D, Karas J, Maharani R, Hughes AB. Total synthesis of theantifungal depsipeptide petriellin A. Journal of Organic Chemistry2011;76(16):6686–93.

Sharma I, Crich D. Direct Fmoc-chemistry-based solid-phase synthesis of peptidylthioesters. Journal of Organic Chemistry 2011;76(16):6518–24.

Larregola M, Lequin O, Karoyan P, Guianvarc’h D, Lavielle S. b-Amino acids containingpeptides and click-cyclized peptide as b-turn mimics: a comparative study with

‘‘conventional’’ lactam- and disulfide-bridged hexapeptides. Journal of PeptideScience 2011;17(9):632–43.

Shi F, Zhang S, Wu S-S, Gao Y, Tu S-J. A diversity-oriented synthesis of pyrazolo[4,3-f]quinoline derivatives with potential bioactivities via microwave-assisted multi-component reactions. Molecular Diversity 2011;15(2):497–505.

Neo AG, Carrillo RM, Delgado J, Marcaccini S, Marcos CF. A multicomponent approachto the synthesis of 1,3-dicarbonylic compounds. Molecular Diversity2011;15(2):529–39.

Chanda K, Chou C-T, Lai J-J, Lin S-F, Yellol GS, Sun C-M. Traceless synthesis ofdiketopiperazine fused tetrahydro-b-carbolines on soluble polymer support.Molecular Diversity 2011;15(2):569–81.

Bararjanian M, Balalaie S, Rominger F, Movassagh B, Bijanzadeh HR. Novel andefficient one-pot five- and six-component reactions for the stereoselectivesynthesis of highly functionalized enaminones and dithiocarbamates. MolecularDiversity 2011;15(2):583–94.

Maiti B, Sun C-M. Novel approach towards the synthesis of skeletally diversebenzimidazole-pyrrolo[1,2-a]quinoxaline by SNAr/Pictet-Spengler reaction underfocused microwave irradiation. New Journal of Chemistry 2011;35(7):1385–96.

Savonnet M, Kockrick E, Camarata A, Bazer-Bachi D, Bats N, Lecocq V, et al.Combinatorial synthesis of metal-organic frameworks libraries by click-chemis-try. New Journal of Chemistry 2011;35(9):1892–7.

Mothia B, Appleyard AN, Wadman S, Tabor AB. Synthesis of peptides containingoverlapping lanthionine bridges on the solid phase: an analogue of rings d and eof the lantibiotic nisin. Organic Letters 2011;13(16):4216–9.

Granger BA, Kaneda K, Martin SF. Multicomponent assembly strategies for thesynthesis of diverse tetrahydroisoquinoline scaolds. Organic Letters2011;13(17):4542–5.

Yarbrough DK, Eckert R, He J, Hagerman E, Qi F, Lux R, et al. Rapid probing of biologicalsurfaces with a sparse-matrix peptide library. PloS One 2011;6(8):e23551.

Kadam A, Buckley SB, Dinh T, Fitzgerald R, Zhang W. Convertible fluorous linkerassisted synthesis of tetrasubstituted furans. Synlett 2011;(11):1608–12.