73466-12-3

Basic information

• Product Name: (-)-LEUKOTRIENE A4 METHYL ESTER
• Synonyms: (-)-LEUKOTRIENE A4 METHYL ESTER;LEUKOTRIENE A4 METHYL ESTER;5S-TRANS-5,6-OXIDO-7E,9E,11Z,14Z-EICOSATETRAENOIC ACID, METHYL ESTER;(-)-leukotriene A4;LEUKOTRIENE A4-METHYLESTER SOLUTION (100UG/ML HEXANE/1% TRIETHYLAMINE);LTA4 (Leukotriene A4 methyl ester);PWXYNAKNLZUYAL-WAQVJNLQSA-N
• CAS NO: 73466-12-3
• Molecular Formula: C₂₁H₃₂O₃
• Molecular Weight: 332.48
• Mol File: 73466-12-3.mol
• Article Data: 20

Chemical Properties

• Appearance: /triethylamine:hexane solution
• Storage Temp.: −20°C
• CAS DataBase Reference: (-)-LEUKOTRIENE A4 METHYL ESTER(CAS DataBase Reference)
• NIST Chemistry Reference: (-)-LEUKOTRIENE A4 METHYL ESTER(73466-12-3)
• EPA Substance Registry System: (-)-LEUKOTRIENE A4 METHYL ESTER(73466-12-3)

Safety Data

• Hazard Codes: F,Xn,N
• Statements: 11-36/37/38-48/20-51/53-62-65-67
• Safety Statements: 9-16-29-33-36/37-61-62
• RIDADR: UN 1208 3/PG 2
• WGK Germany: 2
• Hazardous Substances Data: 73466-12-3(Hazardous Substances Data)

Usage

Description

Leukotriene A4 (LTA4) is synthesized in mast cells, eosinophils, and neutrophils from arachidonic acid by 5-lipoxygenase (5-LO), which exhibits both lipoxygenase and LTA4 synthase activities. LTA4 is rapidly metabolized by LTA4 hydrolase or LTC4 synthase to LTB4 or LTC4, respectively. LTA4, from leukocytes, is known to undergo transcellular metabolism in platelets, erythrocytes, and endothelial cells. Further metabolism of LTA4 by 15-LO leads to lipoxin biosynthesis. LTA4 as a free acid is highly unstable. The methyl ester is stable and can be readily hydrolyzed to the free acid as needed.

Uses

LTA4 (Leukotriene A4 methyl ester) is an unstable intermediate in the biosynthesis of LTB4 and LTC4.

Synthetic route

<(Z)-3-nonenyl>triphenyl phosphonium tosylate (82393-41-7) + (5S,6S)-epoxy-10-formyl-(7E,9E)-decadienoic acid methyl ester (73958-00-6) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
With n-butyllithium In tetrahydrofuran at -78℃;	90%

(5S,6S)-epoxy-10-formyl-(7E,9E)-decadienoic acid methyl ester (73958-00-6) + Phosphorane of (Z)-3-nonen-1-yl-triphenylphosponium bromide (73958-09-5) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide at -78℃;	88%

<(3Z)-nonen-1-yl>triphenylphosphonium iodide (72297-07-5) + (5S,6S)-epoxy-10-formyl-(7E,9E)-decadienoic acid methyl ester (73958-00-6) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.25h; Wittig reaction;	63%
With n-butyllithium In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide
With n-butyllithium 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min; Yield given. Multistep reaction;

(S)-5-hydroperoxy-6-trans,8,11,14-cis-eicosatetraenoic acid methyl ester (75331-81-6) → Leukotriene A4 methyl ester (73466-12-3) + methyl (6E,8Z,11Z,14Z)-5-oxo-6,8,11,14-eicosatetraenoate (74785-00-5)

Conditions	Yield
With 1,2,2,6,6-pentamethylpiperidine; trifluoromethanesulfonic acid anhydride In diethyl ether; dichloromethane at -110℃; for 0.666667h;	A 25% B n/a

diazomethane (186581-53-3, 908094-01-9) + 6-epi-Leukotriene A4 (71548-17-9, 72059-45-1, 74497-09-9, 76375-76-3, 77341-35-6, 114129-55-4, 114129-56-5, 114129-57-6) → Leukotriene A4 methyl ester (73466-12-3) + 5S,6R-6-epi-Leukotriene A4 methyl ester (76738-49-3) + 5R,6S-6-epi-Leukotriene A4 methyl ester (79356-68-6) + 5-epi-6-epi-leukotriene A4 methyl ester (79356-65-3)

Conditions	Yield
In diethyl ether at 0℃; for 0.166667h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

methyl 5(S),6(S)-oxido-11-oxo-7-cis-9-trans-undecadienoate (82442-92-0) + Phosphorane of (Z)-3-nonen-1-yl-triphenylphosponium bromide (73958-09-5) → Leukotriene A4 methyl ester (73466-12-3) + 7-cis-leukotriene A4 methyl ester (82467-14-9)

Conditions	Yield
In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide at -78℃; for 0.333333h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(5S,6S)-epoxy-10-formyl-(7E,9E)-decadienoic acid methyl ester (73958-00-6) + triphenyl <(Z)-non-3-en-1-yl>phosphonium chloride (75415-25-7) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Yield given;

(5S,6S)-epoxy-11,14-eicosadiyne-7E,9E-dienoate (118333-88-3) → Leukotriene A4 methyl ester (73466-12-3) + 13,14-dehydro-leukotriene A4 methyl ester (82850-12-2) + 4-[(2S,3S)-((1E,3E,8Z)-3-Tetradeca-1,3,8-trien-5-ynyl)-oxiranyl]-butyric acid methyl ester (118333-83-8)

Conditions	Yield
With pyridine; hydrogen; Lindlar's catalyst In hexane at 20℃; under 750.06 Torr; Yields of byproduct given;	A 5.5 mg B n/a C n/a
With pyridine; hydrogen; Lindlar's catalyst In hexane at 20℃; under 750.06 Torr; Yield given;	A 5.5 mg B n/a C n/a

(-)-(S,S-trans)-3-(hydroxymethyl)oxiranebutanoic acid methyl ester (73957-99-0) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 68 percent / Py2*CrO3; 4 Angstroem molecular sieves / CH2Cl2 2: CH2Cl2 / 15 h 3: I2 / CH2Cl2 / 1 h 4: 63 percent / nBuLi; HMPA / tetrahydrofuran; hexane / 0.25 h / -78 °C View Scheme
Multi-step reaction with 3 steps 1: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 2: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 3: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 3 steps 1: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 2: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 3: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 3 steps 1: 63 percent / CrO3/Py / CH2Cl2 2: 70 percent 3: 90 percent / n-BuLi / tetrahydrofuran / -78 °C View Scheme
Multi-step reaction with 3 steps 1: 50 percent / Collins oxidation View Scheme

(+)-(S,R-trans)-3-formyloxiranebutanoic acid methyl ester (73427-12-0) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: CH2Cl2 / 15 h 2: I2 / CH2Cl2 / 1 h 3: 63 percent / nBuLi; HMPA / tetrahydrofuran; hexane / 0.25 h / -78 °C View Scheme
Multi-step reaction with 2 steps 1: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 2: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 2 steps 1: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 2: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

7-acetoxy-(5S,6S)-epoxyheptanoic acid methyl ester (76871-82-4) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 69 percent / K2CO3; Na2SO4 / methanol / 0.17 h / 20 °C 2: 68 percent / Py2*CrO3; 4 Angstroem molecular sieves / CH2Cl2 3: CH2Cl2 / 15 h 4: I2 / CH2Cl2 / 1 h 5: 63 percent / nBuLi; HMPA / tetrahydrofuran; hexane / 0.25 h / -78 °C View Scheme

(5S,6S)-epoxy-10-formyl-(9E)-decadienoic acid methyl ester (73958-00-6, 76738-48-2, 77341-38-9, 79356-64-2, 79356-67-5, 82442-92-0, 92009-26-2) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: I2 / CH2Cl2 / 1 h 2: 63 percent / nBuLi; HMPA / tetrahydrofuran; hexane / 0.25 h / -78 °C View Scheme
Multi-step reaction with 2 steps 1: iodine 2: BuLi / tetrahydrofuran; hexamethylphosphoric acid triamide View Scheme

7-acetoxy-(5S,6S)-epoxyheptanoic acid → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: diethyl ether / 0.08 h / 0 °C 2: 69 percent / K2CO3; Na2SO4 / methanol / 0.17 h / 20 °C 3: 68 percent / Py2*CrO3; 4 Angstroem molecular sieves / CH2Cl2 4: CH2Cl2 / 15 h 5: I2 / CH2Cl2 / 1 h 6: 63 percent / nBuLi; HMPA / tetrahydrofuran; hexane / 0.25 h / -78 °C View Scheme

3-nonyn-1-ol (31333-13-8) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 96.4 percent / hydrogen, quinoline / Lindlar catalyst / hexane / 1.25 h 2: 97.1 percent / pyridine / 1.5 h / 0 - 5 °C 3: 95 percent / sodium iodide / acetone / 67 h / Ambient temperature 4: 11.2 g / benzene / 43 h / 80 °C 5: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(Z)-non-3-en-1-ol (10340-23-5) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 97.1 percent / pyridine / 1.5 h / 0 - 5 °C 2: 95 percent / sodium iodide / acetone / 67 h / Ambient temperature 3: 11.2 g / benzene / 43 h / 80 °C 4: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

[(4R,5S)-5-((Z)-3-[1,3]Dioxan-2-yl-propenyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol (85612-85-7) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 9 steps 1: 40.8 g / pyridine / 3 h / 5 °C 2: 100 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 3: 69.4 percent / ozone, oxygen / ethyl acetate / 5 h / -70 °C 4: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 5: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 6: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 7: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 8: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 9: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 9 steps 1: 40.8 g / pyridine / 3 h / 5 °C 2: 100 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 3: 69.4 percent / ozone, oxygen / ethyl acetate / 5 h / -70 °C 4: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 5: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 6: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 7: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 8: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 9: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

3-cis-nonene-1-yl-p-toluenesulfonate (72297-08-6) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / sodium iodide / acetone / 67 h / Ambient temperature 2: 11.2 g / benzene / 43 h / 80 °C 3: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(1’R)-(-)-4,6-O-ethylidene-D-glucose (13224-97-0, 13224-98-1, 13224-99-2, 13225-00-8, 13225-01-9, 13225-02-0, 18465-50-4, 87068-63-1) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 10 steps 1: NaIO4, aq. sodium hydroxide / H2O / 0.25 h / 5 - 10 °C / pH 4 2: 4.7 g / tetrahydrofuran / 0.33 h / -30 °C 3: 2.8 g / triethylamine / CH2Cl2 / 0.75 h / 0 - 5 °C 4: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 5: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 6: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 7: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 8: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 9: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 10: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 10 steps 1: NaIO4, aq. sodium hydroxide / H2O / 0.25 h / 5 - 10 °C / pH 4 2: 4.7 g / tetrahydrofuran / 0.33 h / -30 °C 3: 2.8 g / triethylamine / CH2Cl2 / 0.75 h / 0 - 5 °C 4: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 5: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 6: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 7: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 8: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 9: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 10: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(+)--6-<2-<(benzoyloxy)-1-hydroxy>ethyl>tetrahydro-2H-pyran-2-one (77332-97-9) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 2: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 3: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 4: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 5: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 5 steps 1: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 2: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 3: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 4: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 5: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

Benzoic acid (R)-2-methanesulfonyloxy-2-((S)-6-oxo-tetrahydro-pyran-2-yl)-ethyl ester (77332-98-0) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 2: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 3: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 4: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 4 steps 1: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 2: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 3: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 4: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(+)-(4S-cis)-2,2-dimethyl-5-<(benzoyloxy)methyl>-1,3-dioxolane-4-butanoic acid 3-hydroxypropyl ester (77333-01-8) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 2: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 3: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 4: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 5: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 6: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 6 steps 1: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 2: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 3: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 4: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 5: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 6: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(+)-(4R-cis)-2,2-dimethyl-5-<3-(1,3-dioxan-2-yl)-1-propyl>-1,3-dioxolane-4-methanol benzoate (77333-00-7, 85648-04-0) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: 69.4 percent / ozone, oxygen / ethyl acetate / 5 h / -70 °C 2: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 3: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 4: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 5: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 6: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 7: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 7 steps 1: 69.4 percent / ozone, oxygen / ethyl acetate / 5 h / -70 °C 2: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 3: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 4: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 5: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 6: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 7: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(+)-(4R-cis)(Z)-2,2-dimethyl-5-<3-(1,3-dioxan-2-yl)-1-propenyl>-1,3-dioxolane-4-methanol benzoate (77332-94-6, 77398-80-2) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 8 steps 1: 100 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 2: 69.4 percent / ozone, oxygen / ethyl acetate / 5 h / -70 °C 3: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 4: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 5: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 6: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 7: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 8: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 8 steps 1: 100 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 2: 69.4 percent / ozone, oxygen / ethyl acetate / 5 h / -70 °C 3: 71.9 percent / trifluoroacetic acid / H2O / 3.5 h / 0 °C 4: 5.9 g / triethylamine / CH2Cl2 / 0.75 h / -5 - 0 °C 5: 79.3 percent / potassium carbonate / 7.5 h / 3 - 5 °C 6: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 7: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 8: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(3Z)-3-nonenyliodide (72297-09-7) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 11.2 g / benzene / 43 h / 80 °C 2: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(2R,4S,5R)-4-((E)-3-[1,3]Dioxan-2-yl-propenyl)-2-methyl-[1,3]dioxan-5-ol (85612-90-4) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 8 steps 1: 2.8 g / triethylamine / CH2Cl2 / 0.75 h / 0 - 5 °C 2: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 3: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 4: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 5: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 6: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 7: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 8: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 8 steps 1: 2.8 g / triethylamine / CH2Cl2 / 0.75 h / 0 - 5 °C 2: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 3: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 4: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 5: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 6: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 7: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 8: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

Methanesulfonic acid (R)-2-hydroxy-1-((S)-6-oxo-tetrahydro-pyran-2-yl)-ethyl ester (85612-93-7) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 2: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 3: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 4: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 4 steps 1: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 2: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 3: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 4: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(-)-(2R,4S,5R)-4-<3-(1,3-dioxan-2-yl)propyl>-2-methyl-1,3-dioxan-5-ol methanesulfonate (85612-91-5) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 2: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 3: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 4: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 5: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 6: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 6 steps 1: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 2: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 3: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 4: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 5: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 6: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(2R,4S,5R)(E)-4-<3-(1,3-dioxan-2-yl)-1-propenyl>-2-methyl-1,3-dioxan-5-ol methanesulfonate (85612-89-1) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 2: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 3: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 4: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 5: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 6: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 7: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 7 steps 1: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 2: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 3: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 4: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 5: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 6: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 7: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(-)-(2R,4S,5R)-2-methyl-5-<(methylsulfonyl)oxy>-1,3-dioxane-4-butanoic acid 3-hydroxypropyl ester (85612-92-6) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 2: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 3: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 4: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 5: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 5 steps 1: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 2: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 3: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 4: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 5: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

(1'R)-(-)-2,4-O-ethylidene-D-erythrose (70377-89-8) → Leukotriene A4 methyl ester (73466-12-3)

Conditions	Yield
Multi-step reaction with 9 steps 1: 4.7 g / tetrahydrofuran / 0.33 h / -30 °C 2: 2.8 g / triethylamine / CH2Cl2 / 0.75 h / 0 - 5 °C 3: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 4: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 5: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 6: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 7: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 8: 2.) iodine / 1) CH2Cl2, room temperature, 1 h; 2) CH2Cl2, room temperature, 2.5 h 9: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme
Multi-step reaction with 9 steps 1: 4.7 g / tetrahydrofuran / 0.33 h / -30 °C 2: 2.8 g / triethylamine / CH2Cl2 / 0.75 h / 0 - 5 °C 3: 76.3 percent / hydrogen / platinum oxide / ethyl acetate / 6 h / Ambient temperature 4: 54.5 percent / ozone, oxygen / ethyl acetate / 3 h / -70 °C 5: trifluoroacetic acid, water / 5.5 h / 0 - 5 °C 6: 105 mg / potassium carbonate / 5.5 h / 0 - 5 °C 7: 69.7 percent / pyridine, chromium trioxide / CH2Cl2 / 1) 15 deg C, 15 - 20 min; 2) 15 deg C --> room temperature, 1 h 8: 1.) n-BuLi, 3.) triethylamine, methane sulfonyl chloride / 1) THF, hexane, -78 deg C, 1 h; 2) -78 deg C, 1.75 h, THF, hexane; 3) CH2Cl2, -45 deg C, 20 min 9: 1.) n-BuLi / 1) THF, hexane, -78 deg C, 20 min; 2) HMPA, THF, hexane, -78 deg C, 15 min View Scheme

L-cysteine methyl ester hydrochloride (18598-63-5) + Leukotriene A4 methyl ester (73466-12-3) → leukotriene E4 dimethyl ester (74448-22-9)

Conditions	Yield
With triethylamine In methanol; water for 1h; Ambient temperature; pH 9;	94%
With triethylamine In methanol for 5h; Ring cleavage; Condensation;	75%

Leukotriene A4 methyl ester (73466-12-3) + N-(trifluoroacetyl)-L-cysteinylglycine methyl ester (75290-62-9) → N-trifluoroacetyl-leukotriene D4 dimethyl ester (76322-44-6)

Conditions	Yield
With triethylamine In methanol for 4h; Ring cleavage; Condensation;	77%

Leukotriene A4 methyl ester (73466-12-3) + methyl 6-mercapto-3(E)-hexenoate (135388-27-1) → (7E,9E,11Z,14Z)-(5S,6R)-5-Hydroxy-6-((E)-5-methoxycarbonyl-pent-3-enylsulfanyl)-icosa-7,9,11,14-tetraenoic acid methyl ester (140215-33-4)

Conditions	Yield
With sodium methylate In methanol for 3h; Ambient temperature;	71%

Oxidized glutathione (27025-41-8) + Leukotriene A4 methyl ester (73466-12-3) → Leukotriene C4 methyl ester (73958-10-8)

Conditions	Yield
With triethylamine In methanol for 12h; Condensation; Ring cleavage;	55%

GLUTATHIONE (70-18-8) + Leukotriene A4 methyl ester (73466-12-3) → (7E,9E,11Z,14Z)-(5S,6R)-6-[(R)-2-(4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester

Conditions	Yield
With triethylamine for 2h; Ambient temperature;

3-Dimethylaminopropanethiol (42302-17-0) + Leukotriene A4 methyl ester (73466-12-3) → (7E,9E,11Z,14Z)-(5S,6R)-6-(3-Dimethylamino-propylsulfanyl)-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester (83851-65-4)

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;

1-mercapto-5-carbomethoxy-pentane (20756-86-9) + Leukotriene A4 methyl ester (73466-12-3) → (7E,9E,11Z,14Z)-(5S,6R)-5-Hydroxy-6-(5-methoxycarbonyl-pentylsulfanyl)-icosa-7,9,11,14-tetraenoic acid methyl ester

Conditions	Yield
With sodium methylate In methanol

N-Trifluoroacetylglutathione dimethyl ester (75290-61-8) + Leukotriene A4 methyl ester (73466-12-3) → (6E,8E,10E,14Z)-(S)-5-Hydroxy-12-{(R)-2-(methoxycarbonylmethyl-carbamoyl)-2-[(R)-4-methoxycarbonyl-4-(2,2,2-trifluoro-acetylamino)-butyrylamino]-ethylsulfanyl}-icosa-6,8,10,14-tetraenoic acid methyl ester (76695-80-2, 76740-25-5)

Conditions	Yield
With lithium perchlorate In tetrahydrofuran; diethyl ether at 23℃; for 12h; Yield given;

Leukotriene A4 methyl ester (73466-12-3) + methyl 6-mercapto-3(Z)-hexenoate (140215-41-4) → (7E,9E,11Z,14Z)-(5S,6R)-5-Hydroxy-6-((Z)-5-methoxycarbonyl-pent-3-enylsulfanyl)-icosa-7,9,11,14-tetraenoic acid methyl ester (140215-33-4)

Conditions	Yield
With sodium methylate In methanol Ambient temperature;

Leukotriene A4 methyl ester (73466-12-3) + (S)-4-((R)-2-Mercapto-1-methoxycarbonyl-ethylcarbamoyl)-2-(2,2,2-trifluoro-acetylamino)-butyric acid methyl ester (83851-50-7) → (7E,9E,11Z,14Z)-(5S,6R)-5-Hydroxy-6-{(R)-2-methoxycarbonyl-2-[(S)-4-methoxycarbonyl-4-(2,2,2-trifluoro-acetylamino)-butyrylamino]-ethylsulfanyl}-icosa-7,9,11,14-tetraenoic acid methyl ester (83851-62-1, 84414-54-0)

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;

Leukotriene A4 methyl ester (73466-12-3) + methyl 3-mercaptopropionylglycinate (80115-99-7) → deamino LTD4 dimethyl ester (80116-00-3)

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;	4.2 mg

Leukotriene A4 methyl ester (73466-12-3) + 3-mercaptopropionylglycinedimethylamide (83851-49-4) → (7E,9E,11Z,14Z)-(5S,6R)-6-[2-(Dimethylcarbamoylmethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;	2.3 mg

Leukotriene A4 methyl ester (73466-12-3) + [(3-Mercapto-propyl)-(2,2,2-trifluoro-acetyl)-amino]-acetic acid methyl ester (83851-52-9) → (7E,9E,11Z,14Z)-(5S,6R)-5-Hydroxy-6-{3-[methoxycarbonylmethyl-(2,2,2-trifluoro-acetyl)-amino]-propylsulfanyl}-icosa-7,9,11,14-tetraenoic acid methyl ester (83851-64-3)

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;

Leukotriene A4 methyl ester (73466-12-3) + 4-[(R)-2-Mercapto-1-(methoxycarbonylmethyl-carbamoyl)-ethylcarbamoyl]-butyric acid methyl ester (83851-48-3) → (7E,9E,11Z,14Z)-(5S,6R)-5-Hydroxy-6-[(R)-2-(4-methoxycarbonyl-butyrylamino)-2-(methoxycarbonylmethyl-carbamoyl)-ethylsulfanyl]-icosa-7,9,11,14-tetraenoic acid methyl ester

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;

Leukotriene A4 methyl ester (73466-12-3) + (S)-2-[(R)-3-Mercapto-2-(2,2,2-trifluoro-acetylamino)-propionylamino]-pentanedioic acid dimethyl ester (83851-51-8) → (S)-2-[(R)-3-[(2E,4E,6Z,9Z)-(R)-1-((S)-1-Hydroxy-4-methoxycarbonyl-butyl)-pentadeca-2,4,6,9-tetraenylsulfanyl]-2-(2,2,2-trifluoro-acetylamino)-propionylamino]-pentanedioic acid dimethyl ester (83851-63-2)

Conditions	Yield
With triethylamine In methanol for 3h; Ambient temperature;

Leukotriene A4 methyl ester (73466-12-3) + L-cysteinylglycine → (7E,9E,11Z,14Z)-(5S,6R)-6-[(R)-2-Amino-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester

Conditions	Yield
With triethylamine In methanol; water for 18h; Ambient temperature;

Leukotriene A4 methyl ester (73466-12-3) + glutathione → (7E,9E,11Z,14Z)-(5S,6R)-6-[2-(4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester (73958-10-8, 74841-70-6, 84823-29-0, 84823-30-3, 89461-60-9, 89461-61-0, 89461-62-1, 89461-63-2, 92009-28-4, 113830-70-9, 113830-71-0, 113830-72-1)

Conditions	Yield
With triethylamine In methanol at 23℃; for 5h;

Leukotriene A4 methyl ester (73466-12-3) → leukotriene E4 (75715-89-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 75 percent / Et3N / methanol / 5 h 2: 82 percent / K2CO3 / methanol; H2O / 3.5 h / 0 °C View Scheme

Leukotriene A4 methyl ester (73466-12-3) → leukotriene D4 (73836-78-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 77 percent / Et3N / methanol / 4 h 2: 82 percent / K2CO3 / methanol; H2O / 3.5 h / 0 °C View Scheme

Leukotriene A4 methyl ester (73466-12-3) → (7E,9E,11Z,14Z)-(5S,6R)-6-[(R)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid (73466-14-5, 74841-69-3, 76738-45-9, 79026-71-4, 79026-72-5, 80629-45-4, 82468-64-2, 84823-19-8, 84823-20-1, 87391-79-5, 92009-30-8, 92418-31-0, 92418-46-7, 72025-60-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 55 percent / Et3N / methanol / 12 h 2: 84 percent / K2CO3 / methanol; H2O / 3.5 h / 20 °C View Scheme

Upstream product

• 31333-13-8 3-nonyn-1-ol 
• 73958-00-6 methyl 10-formyl-5,6E-epoxy-7E,9E-decadienoate 
• 73958-09-5 Phosphorane of (Z)-3-nonen-1-yl-triphenylphosponium bromide 
• 73427-12-0 (+)-(S,R-trans)-3-formyloxiranebutanoic acid methyl ester 
• 73957-99-0 (-)-(S,S-trans)-3-(hydroxymethyl)oxiranebutanoic acid methyl ester 
• 118333-88-3 (5S,6S)-epoxy-11,14-eicosadiyne-7E,9E-dienoate 
• 73958-00-6 (5S,6S)-epoxy-10-formyl-(7E,9E)-decadienoic acid methyl ester 
• 75415-25-7 triphenyl <(Z)-non-3-en-1-yl>phosphonium chloride 
• 82442-92-0 methyl 5(S),6(S)-oxido-11-oxo-7-cis-9-trans-undecadienoate 
• 73958-00-6 4-[(2S,3R)-3-((1Z,3E)-5-Oxo-penta-1,3-dienyl)-oxiranyl]-butyric acid methyl ester 
• 63753-78-6 C₃₀H₂₈O₉ 
• 73957-96-7 C₂₅H₂₆O₈ 
• 73957-98-9 C₂₉H₃₀O₉S 
• 73957-95-6 C₃₂H₃₀O₁₀ 

Downstream Products

• 73958-10-8 (7E,9E,11Z,14Z)-(5S,6R)-6-[2-(4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid methyl ester 
• 73958-10-8 Leukotriene C₄ methyl ester 
• 75715-89-8 leukotriene E4 
• 73836-78-9 leukotriene D4 
• 73466-14-5 (7E,9E,11Z,14Z)-(5S,6R)-6-[(R)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid 
• 83058-42-8 Methyl (5S,6Z,8E,10E,12R,14Z)-5,12-Dihydroxyeicosa-6,8,10,14-tetraenoate 
• 72059-45-1 leukotriene A4 
• 73836-78-9 7Z,9E,11E,14Z-LTD₄ 
• 75443-89-9 7Z,9E,11E,14Z-LTE₄ 
• 72025-60-6 5(S)-hydroxy-6(R)-glutathionyl-7,9-E-11,14-Z-eicosatetraenoic acid 
• 72025-60-6 leukotriene C4 
• 72025-60-6 (7E,9Z,11Z,14Z)-(5S,6R)-6-[(S)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid 
• 72025-60-6 (7E,9Z,11Z,14Z)-(5R,6S)-6-[(S)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethylsulfanyl]-5-hydroxy-icosa-7,9,11,14-tetraenoic acid 
• 89461-64-3 7Z,9E,11E,14Z-LTE₄ methyl ester 

Relevant articles and documents

Total synthesis of leukotrienes from butadiene

The total synthesis of leukotrienes has been achieved starting from butadiene by a palladium-catalyzed telomerization at room temperature. A Sharpless catalytic asymmetric epoxidation generated the asymmetric centers with >94% ee. Simple transformations of the key intermediate 15 produced the leukotrienes LTA4 methyl ester (4), LTC4 (1), LTD4 (2) and LTE4 (3), as well as (14S, 15S)-LTA4 methyl ester (24) and the novel [2H2]-LTA4 methyl ester (28). The use of the opposite chiral director in the Sharpless catalytic asymmetric epoxidation gave the key intermediate 15a that has been used in the synthesis of the double epimers of the leukotrienes as well as LTB4.

SYNTHESIS OF TETRADEUTERATED LTA4 METHYL ESTER

Progress in GC/MS coupling in the field of lipids prompted us to prepare deuterated leukotrienes as stable standard compounds.Thus, chiral -tetradeuterated LTA4 methyl ester 4b was synthesized by reduction of the appropriate diyne precursor and will lead to the corresponding tetradeuterated peptidoleukotrienes.

A FACILE STEREOSELECTIVE SYNTHESIS OF LEUKOTRIENE A4(LTA4) METHYL ESTER

A facile synthesis of LTA4 1 methyl ester was achieved according to Scheme 1, in which the key intermediate 6 and 7 were prepared with the new procedures conveniently, stereoselectively and in good yields.