(R)-N-Fmoc-2-(7'-octenyl) alanine

(R)-N-Fmoc-2-(7'-octenyl) alanine Property

Boiling point:

588.3±45.0 °C(Predicted)

Density 

1.140

storage temp. 

-20°C

form 

liquid

pka

3.94±0.41(Predicted)

color 

pale yellow

InChIKey

MADFVGMQNXRFAF-AREMUKBSSA-N

SMILES

C(O)(=O)[C@@](NC(OCC1C2=C(C=CC=C2)C2=C1C=CC=C2)=O)(C)CCCCCCC=C

Safety

Hazard Codes 

N

Risk Statements 

50

Safety Statements 

61

RIDADR 

UN 3077 9 / PGIII

WGK Germany 

3

TSCA 

No

HazardClass 

9

HS Code 

2922498590

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H400Very toxic to aquatic life

Precautionary statements

P273Avoid release to the environment.

(R)-N-Fmoc-2-(7'-octenyl) alanine Chemical Properties,Usage,Production

Uses

(2R)-2-[[(9H-Fluoren-9-ylmethoxy)carbonyl]amino]-2-methyl-9-decenoic Acid, is a stable antimicrobial peptide, that can be isolated from the venom of wild bee Lasioglossum laticeps.

Uses

Olefinic alpha-methyl amino acid for peptide stapling. Upon incorporation of this amino acid into a peptide, along with another of the same or derivative with a different length of the olefinic side chain, the two can be ′stapled′ via a ring closing metathesis reaction with Grubb′s catalyst (product # 579726). The resulting stapled peptide macrocycle has been shown to stabilize the alpha-helical structure of peptides, which can lead to favorable biological characteristics such as increased proteolytic stability and cellular uptake.

reaction suitability

reaction type: Fmoc solid-phase peptide synthesis

Synthesis

1. 1.55 kg (1.0 eq.) of 37-amino-2-methyl-dec-9-enoic acid hydrochloride (XIII) was suspended in 22 L of water and polished and filtered to remove traces of D-BPB hydrochloride. 2. Methyl tert-butyl ether was added and the aqueous product layer was extracted once with methyl tert-butyl ether. 3. The aqueous product layer was added again and 7 L of tetrahydrofuran was added. 4. 20% aqueous sodium carbonate (2.75 eq.) was added to the mixture followed by Fmoc-OSu (0.89 eq.). 5. The reaction was carried out at 20-25 °C, maintaining the pH at 8.5-9.0 by adding additional amounts of 20% sodium carbonate solution until the reaction was complete. 6. Adjust the pH of the mixture to 2.0-2.5 with concentrated hydrochloric acid. 7. The tetrahydrofuran is removed by distillation and methyl tert-butyl ether is added. 8. Separate the layers and wash the organic layer with water 3 times. 9. The organic layer is concentrated in vacuum and azeotropically distilled with methyl tert-butyl ether. 10. The crude oily substance is dissolved in methyl tert-butyl ether, cyclohexylamine (1.10 eq.) is slowly added, and the pH is adjusted to 8.5-9.0. 11. The slurry was stirred at 20-25 °C for 3 h. The solid product salt (XIV) was isolated by filtration. 12. The solids were rinsed twice with methyl tert-butyl ether and the wet cake was reloaded into a clean reactor. 13. The wet cake was recrystallized with tetrahydrofuran and methyl tert-butyl ether to improve purity. 14. The solid salt is suspended in methyl tert-butyl ether and water and the pH is adjusted to 2.0-2.5 with 25% sulfuric acid. 15. The organic product layer was washed with water until no cyclohexylamine remained. 16. The organic layer was concentrated and azeotropically distilled with hexane to a loose oil. 17. 17. The product (IIa) was crystallized from chloroform and hexane and purged dry with 1.0 cfm nitrogen at <0 °C. The product (IIa) was then purged dry at <0 °C with 1.0 cfm nitrogen. Yield: 1.12 kg, 41.5% yield. Recrystallization procedure: 18. Acetonitrile (23 mL/10 g of raw material ((R)-Ala-Ni-BPB(XI) in oil)) was added to the crude product and the mixture was heated to 70 °C and held for 30 min, then cooled to 20 °C. The mixture was purified with aqueous nitrogen. 19. The mixture was filtered and the solids were washed with acetonitrile (5 mL) and methyl tert-butyl ether (8.5 mL) to give a crystalline product.

References

[1] Patent: US2014/128581, 2014, A1. Location in patent: Paragraph 0087; 0156; 0157