siderophores: amphibactin-t and moanachelin ala-b 7klv of ... · bschool of chemistry, yachay tech,...

S1

An Efficient Solid-Phase Strategy for Total Synthesis of Naturally Occurring Amphiphilic Marine

Siderophores: Amphibactin-T and Moanachelin ala-B

Prabhakar Cherkupally,a Suhas Ramesh,a Thavendran Govender,a Hendrik G.

Kruger,a Beatriz G. de la Torre,a,b* Fernando Albericioa,b,c,d,e,f*

aCatalysis and Peptide Research Unit, School of Health Sciences, University of Kwazulu-Natal,

Durban 4001, South AfricabSchool of Chemistry, Yachay Tech, Yachay City of Knowledge, 100119-Urcuqui, EcuadorcSchool of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South AfricadInstitute for Research in Biomedicine-Barcelona (IRB-Barcelona), 08028-Barcelona, SpaineCIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine,

Barcelona Science Park, 08028 Barcelona, SpainfDepartment of Organic Chemistry, University of Barcelona, 08028-Barcelona, Spain

e-mails: Albericio@ukzn.ac.za; falbericio@yachaytech.edu.ec; albericio@irbbarcelona.org (FA)

and bgarcia@yachaytech.edu.ec (BGT)

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2015

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S2 Table of contents

S3 Crude HPLC profile of Fmoc-L-Orn-OBn▪TFA (3)

S4 1H NMR & 13C NMR copies of Fmoc-L-Orn-OBn▪TFA (3)

S5 HRMS (ESI-QTOF) profile of Fmoc-L-Orn-OBn▪TFA (3)

S6 1H NMR & 13C NMR copies of Fmoc-L-Orn(Ac,OBz)-OBn (4)

S7 HRMS (ESI-QTOF) profile of Fmoc-L-Orn(Ac,OBz)-OBn (4)

S8 1H NMR & 13C NMR copies of Fmoc-L-Orn(Bz)-OBn (5)

S9 HRMS (ESI-QTOF) profile of Fmoc-L-Orn(Bz)-OBn (5)

S10 1H NMR & 13C NMR copies of Fmoc-L-Orn(Ac,OBz)-OH (1)

S11 HRMS (ESI-QTOF) profile of Fmoc-L-Orn(Ac,OBz)-OH (1)

S12 LCMS profiles of model peptide ‘DA-Lys-Ser-Orn(Ac,OH)-OH’

S13 Purified HPLC profile of amphibactin-T

S14 HRMS (ESI-QTOF) profile of amphibactin-T

S15 Purified HPLC profile of moanachelin ala-B

S16 HRMS (ESI-QTOF) profile of moanachelin ala-B

S3

Crude HPLC profile of Fmoc-L-Orn-OBn▪TFA (3)

HPLC ConditionsColumn: Phenomenex column C18 (3 µm x 4.6 x 50 mm)Eluent: 5 - 95% CH3CN / 0.1% TFA　in 15 min Sol. A:100% H2O/0.1% TFA, Sol. B: 100% CH3CN/0.1% TFAWavelength: 220 nm Flow rate: 1 mL/ min

8.684

S4

1H NMR & 13C NMR copies of Fmoc-L-Orn-OBn▪TFA (3)

H2O

S5

HRMS (ESI-QTOF) profile of Fmoc-L-Orn-OBn▪TFA (3); Calc. for C27H28N2O4 445.2121,

found 445.2167.

S6

1H NMR & 13C NMR copies of Fmoc-L-Orn(Ac,OBz)-OBn (4)

H2O

S7

HRMS (ESI-QTOF) profile of Fmoc-L-Orn(Ac,OBz)-OBn (4); Calc. for C36H34N2O7 607.2438,

found 607.2403.

S8

1H NMR & 13C NMR copies of Fmoc-L-Orn(Bz)-OBn (5)

H2O

S9

HRMS (ESI-QTOF) profile of Fmoc-L-Orn(Bz)-OBn (5); Calc. for C34H32N2O5 549.2383, found

549.2342.

S10

1H NMR & 13C NMR copies of Fmoc-L-Orn(Ac,OBz)-OH (1)

H2O

S11

HRMS (ESI-QTOF) profile of Fmoc-L-Orn(Ac,OBz)-OH (1); Calc. for Calc. for C29H28N2O7

517.1969, found 517.1975.

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Model peptide: DA-Lys-Ser-Orn(Ac,OBz)-OH; Calc. for C33H53N5O9 663.3843, found 664;

DA-Lys-Ser-Orn(Ac,OH)-OH; Calc. for C26H49N5O8 559.3581, found 560 (M+1).

530 540 550 560 570 580 590 600 610 620 630 640 650 660 670 680 690 m/z0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

Inten.(x10,000,000)

664

560

561

450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 m/z0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

Inten.(x1,000,000)

560

DA-Lys-Ser-Orn(Ac,OH)-OH

DA-Lys-Ser-Orn(Ac,OH)-OH

DA-Lys-Ser-Orn(Ac,OBz)-OH

LCMS profile of crude model peptide after debenzoylation with 25% NH3 in MeOH

LCMS profile of crude model peptide after debenzoylation

with 1 M LiOH in THF/MeOH

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Purified HPLC profile of amphibactin-T

Prep-HPLC ConditionsColumn: Phenomenex C18 column (10 µm x 10 x 250 mm)Eluent: 5 - 60% CH3CN / 0.1% TFA　in 30 min Sol. A: 100% H2O/0.1% TFA, Sol. B: 100% CH3CN/0.1% TFAWavelength: 220 nm Flow rate: 7 mL/ min

8.862

S14

HRMS (ESI-QTOF) profile of amphibactin-T; Calc. for C36H65N7O13 804.4713, found

804.4707.

S15

Purified HPLC profile of moanachelin ala-B

Prep-HPLC ConditionsColumn: Phenomenex C18 column (10 µm x 10 x 250 mm)Eluent: 5 - 60% CH3CN / 0.1% TFA　in 30 min Sol. A: 100% H2O/0.1% TFA, Sol. B: 100% CH3CN/0.1% TFAWavelength: 220 nm Flow rate: 7 mL/ min

9.045

S16

HRMS (ESI-QTOF) profile of moanachelin ala-B; Calc. for C36H65N7O12 788.4763, found

788.4770.