3913-67-5

Basic information

• Product Name: N-Methyl-L-alanine
• Synonyms: N-METHYL-L-ISOLEUCINE HYDROCHLORIDE;N-ME-ILE-OH HCL;N-ALPHA-METHYL-L-ISOLEUCINE HYDROCHLORIDE;H-L-MELLE-OH HCL;H-MEILE-OH HCL;H-MEILE-OH+ HCL;Alanine, N-methyl-, L-;alpha-(Methylamino)propionic acid
• CAS NO: 3913-67-5
• Molecular Formula: C₄H₉NO₂
• Molecular Weight: 103.12
• EINECS: 1533716-785-6
• Product Categories: Amino Acid Derivatives;N-Methyl Amino Acids;N-Methyl Amino Acids;Peptide Synthesis;Unnatural Amino Acid Derivatives;amino acids
• Mol File: 3913-67-5.mol
• Article Data: 41

Chemical Properties

• Melting Point: 315-317 °C (decomp)
• Boiling Point: 190.1 °C at 760 mmHg
• Flash Point: 68.8 °C
• Appearance: /
• Density: 1.048 g/cm³
• Refractive Index: 1.405
• Storage Temp.: Store at RT.
• Solubility: Aqueous Acid (Slightly), Water (Slightly)
• PKA: 2.32±0.10(Predicted)
• BRN: 1720922
• CAS DataBase Reference: N-Methyl-L-alanine(CAS DataBase Reference)
• NIST Chemistry Reference: N-Methyl-L-alanine(3913-67-5)
• EPA Substance Registry System: N-Methyl-L-alanine(3913-67-5)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 3913-67-5(Hazardous Substances Data)

Usage

Chemical Properties

White to off-white powder

Uses

N-Methyl-L-alanine is a reactant used in the preparation of site-specific trastuzumab maytansinoid antibody-drug conjugates with improved therapeutic activity.

Definition

ChEBI: A methyl-L-alanine in which one of the the amino hydrogen of L-alanine is replaced by a methyl group.

InChI:InChI=1/C5H11NO/c1-4(6-3)5(2)7/h4,6H,1-3H3/t4-/m0/s1

Synthetic route

(2R,2'R)-N-<2'-(methylamino)propionyl>bornane-10,2-sultam → N-methylalanine (3913-67-5) + N-methyl-D-alanine (29475-64-7)

Conditions	Yield
With lithium hydroxide In tetrahydrofuran at 0℃; Title compound not separated from byproducts;	A n/a B 94%

(2S,2'S)-N-<2'-(methylamino)propionyl>bornane-10,2-sultam → N-methylalanine (3913-67-5)

Conditions	Yield
With lithium hydroxide In tetrahydrofuran at 0℃;	91%

(S)-2-(Benzhydryl-methyl-amino)-propionic acid benzhydryl ester → N-methylalanine (3913-67-5)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol	91%

formaldehyd (50-00-0) + L-alanin (56-41-7) → N-methylalanine (3913-67-5)

Conditions	Yield
With sodium dihydrogenphosphate; zinc at 30℃; for 0.25h;	85%

(2R)-2-(4-Toluenesulfonyloxy)propionic Acid (130368-69-3) + methylamine (74-89-5) → N-methylalanine (3913-67-5)

Conditions	Yield
In water at 15 - 30℃; Autoclave; Sealed tube;	81.4%

R-(+)-2-bromopropionic acid (10009-70-8) + methylamine (74-89-5) → N-methylalanine (3913-67-5)

Conditions	Yield
In water
With lead(II) hydroxide on calcium carbonate; water

N-(tert-butoxycarbonyl)-N-methyl-L-alanine (16948-16-6) → N-methylalanine (3913-67-5)

Conditions	Yield
With trifluoroacetic acid

Nα-4-toluenesulfonyl-Nα-methylalanine (79821-69-5) → N-methylalanine (3913-67-5)

Conditions	Yield
With hydrogen bromide; acetic acid

(S)-2-[Methyl-(toluene-4-sulfonyl)-amino]-propionic acid isopropyl ester (60522-13-6) → N-methylalanine (3913-67-5)

Conditions	Yield
With hydrogen bromide; phenol
With hydrogen bromide; phenol In water for 0.5h; Heating;

(-)-N-methyl-N-benzyl-(S)-Ala (63238-82-4) → N-methylalanine (3913-67-5)

Conditions	Yield
With hydrogen; palladium on activated charcoal In acetic acid

N-Chloracetyl-N-methyl-DL-alanin (138062-74-5) → N-methylalanine (3913-67-5)

Conditions	Yield
In water at 30℃; N-Acyl-L-prolin-Acylase; other substrates, enantioselectivity;
With hydrogenchloride In water at 30℃; N-Acyl-L-prolin-Acylase, pH 7.0;

theonellamine B (105091-14-3, 119816-11-4) → N-methylalanine (3913-67-5) + L-valine (72-18-4) + L-threonine (72-19-5) + N-methyl-L-valine (2480-23-1)

Conditions	Yield
With hydrogenchloride at 110℃; for 40h; Further byproducts given;

theonellamine B (105091-14-3, 119816-11-4) → N-methylalanine (3913-67-5) + L-valine (72-18-4) + L-threonine (72-19-5) + N-methyl-L-valine (2480-23-1) + (R)-leucine (328-38-1) + 3-amino propanoic acid (107-95-9)

Conditions	Yield
With hydrogenchloride at 110℃; for 4h;

theonellamine B (105091-14-3, 119816-11-4) → N-methylalanine (3913-67-5) + L-valine (72-18-4) + N-methyl-L-valine (2480-23-1) + 3-amino propanoic acid (107-95-9)

Conditions	Yield
With hydrogenchloride at 110℃; for 40h; Further byproducts given;

(S)-2-[(2-Chloro-acetyl)-methyl-amino]-propionic acid (138062-73-4) → N-methylalanine (3913-67-5)

Conditions	Yield
With hydrogenchloride In water at 30℃; N-Acyl-L-prolin-Acylase, pH 7.0;

(S)-2-[Methyl-(2,2,5,7,8-pentamethyl-chroman-6-sulfonyl)-amino]-propionic acid benzyl ester → N-methylalanine (3913-67-5)

Conditions	Yield
With hydrogen bromide; acetic acid

phenylmethyl (4S)-5-oxo-4-methyl-1,3-oxazolidine-3-carboxylate (37661-60-2) → N-methylalanine (3913-67-5)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol Yield given;

N-p-toluenesulfonyl-N-methyl-d-alanine → N-methylalanine (3913-67-5)

Conditions	Yield
With hydrogenchloride at 100℃;

hydrogenchloride (7647-01-0) + Nα-4-toluenesulfonyl-Nα-methylalanine (79821-69-5) → N-methylalanine (3913-67-5) + toluene-4-sulfonic acid (104-15-4)

Conditions	Yield
at 100℃;

N-benzyloxycarbonyl-L-phenylalanyl-N-methyl-L-alanine (352199-36-1) → N-methylalanine (3913-67-5) + N-Cbz-L-Phe (1161-13-3)

Conditions	Yield
With carboxypeptidase-Y In water at 37℃; pH=6.5; Kinetics;
With hydrogenchloride; carboxypeptisae-A In water at 37℃; pH=6.5; Enzyme kinetics; Kinetics; Further Variations:; Reagents;

(2S)-2-(methyl{[(phenylmethyl)oxy]carbonyl}amino)propanoic acid (21691-41-8) → N-methylalanine (3913-67-5)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol; water at 20℃; for 20h;
With ethylenediaminetetraacetic acid; phenylmethylsulphonyl fluoride; water In aq. phosphate buffer at 30℃; Kinetics; Reagent/catalyst; Microbiological reaction; Enzymatic reaction;

apratoxin E → N-methylalanine (3913-67-5) + N-methyl-L-isoleucine (4125-98-8) + O-Methyltyrosine (6230-11-1) + L-tyrosine (60-18-4) + L-proline (147-85-3)

Conditions	Yield
With hydrogenchloride; water at 110℃; for 18h;

itralamide A (1187486-24-3) → L-alanin (56-41-7) + N-methylalanine (3913-67-5) + N-methyl-L-valine (2480-23-1) + (2S,3R)-3-hydroxy-2-(methylamino)butanoic acid (2812-28-4) + N-methylvalylalanine + N-methylphenylalanylalanine + N-methyl-D-phenylalanine (56564-52-4)

Conditions	Yield
With hydrogenchloride; water at 110℃; for 18.5h;

itralamide B (1187486-25-4) → N-methylalanine (3913-67-5) + D-Val-OH (640-68-6) + (2S,3R)-3-hydroxy-2-(methylamino)butanoic acid (2812-28-4) + N-methylalanylvaline + N-methylphenylalanylvaline + N-methyl-D-phenylalanine (56564-52-4)

Conditions	Yield
With hydrogenchloride; water at 110℃; for 18.5h;

aspochracin → N-methylalanine (3913-67-5) + N-methyl-L-valine (2480-23-1) + L-ornithine (70-26-8)

Conditions	Yield
With hydrogenchloride; water at 110℃; for 20h;

sclerotiotide A (1232889-28-9) → N-methylalanine (3913-67-5) + L-valine (72-18-4) + L-ornithine (70-26-8)

Conditions	Yield
With hydrogenchloride; water at 110℃; for 20h;

sclerotiotide B (1232889-32-5) → N-methylalanine (3913-67-5) + N-methyl-L-valine (2480-23-1) + L-ornithine (70-26-8)

Conditions	Yield
With hydrogenchloride; water at 110℃; for 20h;

sclerotiotide C (1232889-36-9) → N-methylalanine (3913-67-5) + N-methyl-L-valine (2480-23-1) + L-lysine (56-87-1)

Conditions	Yield
With hydrogenchloride; water at 110℃; for 20h;

7,39-epi-Lagunamide A (1255709-51-3) → L-alanin (56-41-7) + N-methylalanine (3913-67-5) + D-allo-isoleucine (1509-34-8) + L-isoleucine (73-32-5) + (2R,3S)-2-hydroxy-3-methylpentanoic acid (488-15-3, 51576-04-6, 59653-35-9, 86540-81-0, 86630-77-5, 70748-47-9) + N-methyl-D-phenylalanine (56564-52-4)

Conditions	Yield
With hydrogenchloride; water at 110℃; for 18h; sealed vial;

ethanol (64-17-5) + N-methylalanine (3913-67-5) → (S)-2-methylaminopropionic acid ethyl ester hydrochloride (117856-39-0)

Conditions	Yield
With thionyl chloride for 22h; Ambient temperature;	100%
With hydrogenchloride In 1,4-dioxane for 18h;
With thionyl chloride In neat (no solvent) at 0 - 25℃; for 16h;
With thionyl chloride at 0 - 25℃; for 16h;	1.8 g
With thionyl chloride at 0 - 25℃; for 16h;

methanol (67-56-1) + N-methylalanine (3913-67-5) → N-methyl-L-alanine methyl ester hydrochloride (19914-41-1, 20045-77-6, 114079-50-4)

Conditions	Yield
With thionyl chloride at 20℃; for 96h;	100%
With thionyl chloride

N-methylalanine (3913-67-5) → N-methyl-L-alanine methyl ester hydrochloride (19914-41-1, 20045-77-6, 114079-50-4)

Conditions	Yield
In methanol	100%

N-methylalanine (3913-67-5) + 1,1'-Thiocarbonyldiimidazole (6160-65-2) → 3,4-dimethyl-2-thioxo-oxazolidin-5-one

Conditions	Yield
In dichloromethane at 0 - 20℃; Inert atmosphere;	91%

N-methylalanine (3913-67-5) + C45H62N4O13 → C49H69N5O14

Conditions	Yield
Stage #1: C45H62N4O13 With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide for 0.166667h; Stage #2: N-methylalanine In N,N-dimethyl-formamide for 1h;	91%

N-methylalanine (3913-67-5) + acetone (67-64-1) → N-isopropyl-N-methyl-L-alanine (1105044-89-0)

Conditions	Yield
With hydrogen; palladium 10% on activated carbon In methanol under 775.743 Torr; for 18h;	88%
With hydrogen; palladium 10% on activated carbon In methanol under 775.743 Torr; for 18h;	88%

N-methylalanine (3913-67-5) → carbon dioxide (124-38-9) + acetaldehyde (75-07-0) + methylamine (74-89-5)

Conditions	Yield
With hydrogenchloride; sodium hydroxide; sodium perchlorate; chlorine at 24.9℃; Mechanism; Rate constant; Equilibrium constant; multistep reaction: 1.) water, 298 deg K, 2.) water, 298 deg K; reactions under var. conditions;	A n/a B 87% C n/a

N-methylalanine (3913-67-5) + Allyl chloroformate (2937-50-0) → Alloc-Me-Ala

Conditions	Yield
With sodium hydroxide In tetrahydrofuran; water at 20℃; for 3h;	87%

N-methylalanine (3913-67-5) + di-tert-butyl dicarbonate (24424-99-5) → N-(tert-butoxycarbonyl)-N-methyl-L-alanine (16948-16-6)

Conditions	Yield
With sodium hydroxide In diethyl ether; water at 0 - 20℃; for 16h;	86%
With sodium hydroxide In 1,4-dioxane; water for 5h; Ambient temperature;	42.3%

N-methylalanine (3913-67-5) + methyl chloroformate (79-22-1) → 2-(methoxycarbonylmethylamino)propionic acid (1085528-19-3)

Conditions	Yield
Stage #1: N-methylalanine With sodium hydroxide In water at 3℃; for 0.5h; Inert atmosphere; Stage #2: methyl chloroformate In water at 3℃; for 6.5h; Stage #3: With hydrogenchloride In water at 20℃; pH=1;	86%
With sodium carbonate; sodium hydroxide In water at 0 - 20℃; for 7.25h;	77%

[ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 (52462-29-0) + N-methylalanine (3913-67-5) → [(p-cymene)RuCl(η(2)-N,O-NH(CH3)CH(CH3)COO] (675141-34-1)

Conditions	Yield
With sodium methylate In methanol; dichloromethane byproducts: NaCl; soln. of 2 equiv. of N-Me-alanine and 1 equiv. of NaOMe in MeOH added dropwise to soln. 1 equiv. of complex in CH2Cl2, mixt. stirred for 3 h at room temp.; solvent distd. in vac., residue dissolved in CH2Cl2, NaCl centrifuged, soln. added dropwise to pentane, ppt. washed twice with Et2O then pentane, elem. anal.;	81%

N-methylalanine (3913-67-5) + 3-iodobenzonitrile (69113-59-3) → N-(3-cyanophenyl)-methyl-L-alanine (1335533-53-3)

Conditions	Yield
With copper(l) iodide; caesium carbonate In dimethyl sulfoxide; N,N-dimethyl-formamide at 160℃; for 0.75h; Microwave irradiation;	81%

N-methylalanine (3913-67-5) + 2,4-dichloro-6-isopropylpyrimidin-5-amine → (7S)-2-chloro-4-isopropyl-7,8-dimethyl-7,8-dihydropteridin-6(5H)-one

Conditions	Yield
With sodium hydrogencarbonate In ethanol at 90℃; for 16h;	81%

N-methylalanine (3913-67-5) + 1H,2H,4H-thieno[2,3-d][1,3]oxazine-2,4-dione (103979-54-0) → (S)-3,4-dihydro-3,4-dimethyl-1H-thieno[2,3-e][1,4]diazepine-2,5-dione (1140528-73-9)

Conditions	Yield
In water Reflux; regioselective reaction;	80%

phosgene (75-44-5) + N-methylalanine (3913-67-5) → (L)-3,4-dimethyl-1,3-oxazolidine-2,5-dione (58311-53-8)

Conditions	Yield
In tetrahydrofuran at 50℃; for 4h; Inert atmosphere;	77.6%
Product distribution / selectivity;

5-amino-2,4-dichloro-6-methylpyrimidine (13162-27-1) + N-methylalanine (3913-67-5) → (7S)-2-chloro-4,7,8-trimethyl-7,8-dihydropteridin-6(5H)-one

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water Reflux;	77%

bis[dichloro(pentamethylcyclopentadienyl)iridium(III)] (12354-84-6, 12354-85-7) + N-methylalanine (3913-67-5) → [Cp(*)IrCl(η(2)-N,O-NH(CH3)CH(CH3)COO] (675585-20-3, 675141-32-9)

Conditions

Yield

With sodium methylate In methanol; dichloromethane byproducts: NaCl; soln. of 2 equiv. of N-Me-alanine and 1 equiv. of NaOMe in MeOH added dropwise to soln. 1 equiv. of complex in CH2Cl2, mixt. stirred for 3 h at room temp.; solvent distd. in vac., residue dissolved in CH2Cl2, NaCl centrifuged, soln. added dropwise to pentane, ppt. washed twice with Et2O then pentane, elem. anal.; isomers detected by (1)H and (13)C NMR;

76%

5-amino-2,4-dichloropyrimidine (5177-27-5) + N-methylalanine (3913-67-5) → (7S)-2-chloro-7,8-dimethyl-7,8-dihydropteridin-6(5H)-one

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 80℃; for 3h;	75%

N-methylalanine (3913-67-5) + (fluorenylmethoxy)carbonyl chloride (28920-43-6) → N-(9-fluorenylmethoxycarbonyl)-N-methyl-L-alanine (84000-07-7)

Conditions	Yield
With sodium carbonate In tetrahydrofuran at 20℃; for 6h;	74.9%

{(nBu3P)(Cl)Pd(μ-Cl)}2 + N-methylalanine (3913-67-5) → [(nBu3P)PdCl(η(2)-N,O-NH(CH3)CH(CH3)COO] (675141-35-2, 675585-26-9)

Conditions	Yield
With sodium methylate In methanol; dichloromethane byproducts: NaCl; soln. of 2 equiv. of N-Me-alanine and 1 equiv. of NaOMe in MeOH added dropwise to soln. 1 equiv. of complex in CH2Cl2, mixt. stirred for 3 h at room temp.; solvent distd. in vac., residue dissolved in CH2Cl2, NaCl centrifuged, soln. added dropwise to pentane, ppt. washed twice with Et2O then pentane, elem. anal.;	71%

N-methylalanine (3913-67-5) + 2-<(3-phenyl-2-propynyl)oxy>benzaldehyde (73179-67-6) → 1,2-dimethyl-3-phenyl-1,2,4,9b-tetrahydro-5-oxa-1-aza-cyclopenta[a]naphthalene (637759-97-8)

Conditions	Yield
lk In toluene for 4h; Heating;	68%

dichlorobis(triethyl phosphine)-μ-dichloro dipalladium (II) + N-methylalanine (3913-67-5) → [(Et3P)PdCl(η(2)-N,O-NH(CH3)CH(CH3)COO] (675141-36-3, 675585-28-1)

Conditions

Yield

With sodium methylate In methanol; dichloromethane byproducts: NaCl; soln. of 2 equiv. of N-Me-alanine and 1 equiv. of NaOMe in MeOH added dropwise to soln. 1 equiv. of complex in CH2Cl2, mixt. stirred for 3 h at room temp.; solvent distd. in vac., residue dissolved in CH2Cl2, NaCl centrifuged, soln. added dropwise to pentane, ppt. washed twice with Et2O then pentane, elem. anal.; isomers detected by (1)H and (13)C NMR;

68%

N-methylalanine (3913-67-5) + (4-nitrophenyl) N-[4-(trifluoromethyl)-2-pyridyl]carbamate → (5S)-1,5-dimethyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidine-2,4-dione

Conditions	Yield
In 1,4-dioxane at 80℃; Inert atmosphere;	67%

N-methyl-N-[(3-methyldithio)-1-oxopropyl]-L-alanine (138148-62-6) + 5-methyldithio-pentanoic acid (138148-67-1) + N-methylalanine (3913-67-5) + isobutyl chloroformate (543-27-1) → N-methyl-N-(5-methyldithio-pentanoyl)-L-alanine

Conditions	Yield
With triethylamine In tetrahydrofuran; water	66%
With triethylamine In tetrahydrofuran; water	66%

n-dodecanoyl chloride (112-16-3) + N-methylalanine (3913-67-5) → N-n-Dodecanoyl-N-methyl-(S)-alanine

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide	64%
With triethylamine In N,N-dimethyl-formamide at 0℃; for 6h;	64%

Upstream product

• 7647-01-0 hydrogenchloride 
• 79821-69-5 N^α-4-toluenesulfonyl-N^α-methylalanine 
• 127-17-3 2-oxo-propionic acid 
• 74-89-5 methylamine 
• 130368-69-3 (2R)-2-(4-Toluenesulfonyloxy)propionic Acid 
• 302-72-7 rac-Ala-OH 
• 1334149-94-8 apratoxin S₄ 

Downstream Products

• 35023-55-3 N-methyl-L-alanine methyl ester 
• 88061-66-9 N-methyl-D-alanine methyl ester 
• 194736-56-6 L-FDAA-L-N-methylalanine 
• 38378-03-9 N-Nitroso-N-methyl-L-alanin 
• 58311-53-8 (S)-3,4-dimethyloxazolidine-2,5-dione 
• 84000-07-7 N-(9-fluorenylmethoxycarbonyl)-N-methyl-L-alanine 
• 2749-11-3 (S)-Alaninol 
• 1571105-54-8 C₅₈H₉₀N₁₂O₁₀ 
• 1571105-51-5 C₆₀H₉₄N₁₂O₁₀ 
• 1571105-47-9 C₅₉H₉₂N₁₂O₁₀ 
• 1571105-46-8 C₅₉H₉₀N₁₂O₁₀ 
• 1571105-45-7 C₅₉H₈₉N₁₁O₁₀ 
• 1571105-44-6 C₅₈H₈₈N₁₂O₁₀ 
• 1571105-52-6 C₅₈H₉₂N₁₂O₁₀ 

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