1404-64-4

Basic information

• Product Name: SPARSOMYCIN
• Synonyms: nsc59729;sparsomycin;Sparsomycin from Streptomyces sparsogenes;(E)-N-[(S)-1-(Hydroxymethyl)-2-[[(methylthio)methyl]sulfinyl]ethyl]-3-(1,2,3,4-tetrahydro-6-methyl-2,4-dioxopyrimidine-5-yl)propenamide;U-19183;2-Propenamide, N-[(1S)-1-(hydroxymethyl)-2-[(R)-[(methylthio)methyl]sulfinyl]ethyl]-3-(1,2,3,4-tetrahydro-6-methyl-2,4-dioxo-5-pyrimidinyl)-, (2E)-;Aids012106;Aids-012106
• CAS NO: 1404-64-4
• Molecular Formula: C₁₃H₁₉N₃O₅S₂
• Molecular Weight: 361.441
• Mol File: 1404-64-4.mol
• Article Data: 5

Chemical Properties

• Melting Point: 208-209° (dec)
• Appearance: /
• Density: 1.3893 (rough estimate)
• Refractive Index: 1.6390 (estimate)
• Storage Temp.: 2-8°C
• PKA: 8.67 in water, 9.05 in 40% ethanol
• CAS DataBase Reference: SPARSOMYCIN(CAS DataBase Reference)
• NIST Chemistry Reference: SPARSOMYCIN(1404-64-4)
• EPA Substance Registry System: SPARSOMYCIN(1404-64-4)

Safety Data

• Hazard Codes: T+
• Statements: 28
• Safety Statements: 28-36/37-45
• RIDADR: UN 2811 6.1/PG 2
• RTECS: WG5850000
• Hazardous Substances Data: 1404-64-4(Hazardous Substances Data)

Usage

Description

Sparsomycin is a bacterial metabolite and a nucleoside analog of uracil, derived from S. sparsogenes, which exhibits a range of biological activities. It is known for its ability to inhibit peptidyl transferase, interfere with tRNA binding, and reduce tumor growth in various models. Sparsomycin is active against KB carcinoma cells, Gram-positive and Gram-negative bacteria, and fungi, making it a versatile compound with potential applications in medicine and research.

Uses

Used in Antibacterial Applications:
Sparsomycin is used as an antibiotic for its ability to inhibit protein synthesis in bacteria, including both Gram-positive and Gram-negative strains. This makes it a valuable tool in the fight against bacterial infections.
Used in Antifungal Applications:
Sparsomycin is also used as an antifungal agent, effective against various fungal species, which can be crucial in treating fungal infections.
Used in Anticancer Applications:
Sparsomycin is used as an anticancer agent, particularly in reducing tumor growth in models such as P388 mouse leukemia and Walker 256 carcinosarcoma rat models. Its ability to inhibit protein synthesis in cancer cells makes it a promising candidate for cancer treatment.
Used in Research:
Sparsomycin is used as a research tool for studying protein biosynthesis, specifically in the context of its interaction with the peptidyltransferase center of the ribosome. This helps researchers understand the mechanisms of protein synthesis and develop new strategies for targeting this process in various diseases.
Used in Drug Development:
Sparsomycin's unique mechanism of action as an inhibitor of peptidyl transferase makes it a potential candidate for the development of new drugs targeting protein synthesis in various pathogens and cancer cells.

InChI:InChI=1/C13H19N3O5S2/c1-8-10(12(19)16-13(20)14-8)3-4-11(18)15-9(5-17)6-23(21)7-22-2/h3-4,9,17H,5-7H2,1-2H3,(H,15,18)(H2,14,16,19,20)/b4-3+

Synthetic route

O-(methoxymethyl)sparsomycin (95407-15-1) → sparsomycin (1404-64-4)

Conditions	Yield
With Dowex(R) 50W H(1+) form In methanol at 50℃; for 2h;	74%
With methanol; Dowex 50W at 50℃;	73%
With hydrogenchloride In methanol at 50℃; for 5h;	65%

L-Cysteine (52-90-4) + L-Tryptophan (73-22-3) → sparsomycin (1404-64-4)

Conditions	Yield
With Streptomyces sparsogenes var. sparsogenes at 32℃; for 240h; Mechanism; Streptomyces sparsogenes var. spartogenes; other labeled (2)H and (13)C educts;

S-Oxo-S<(methylthio)methyl>-D-cysteinol (77826-38-1) + (E)-β-(2,4-Dioxo-6-methyl-1,2,3,4-tetrahydropyrimidin-5-yl)acrylic acid (28277-67-0) → sparsomycin (1404-64-4)

Conditions	Yield
With chloroformic acid ethyl ester; triethylamine 1.) THF/DMF, 0 deg C, 4 h; 2.) THF/DMF, room temp., 48 h; Yield given. Multistep reaction;

(RS)-O-(methoxymethyl)-S-((methylthio)methyl)-D-cysteinol S-oxide (95407-13-9) → sparsomycin (1404-64-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 88 percent / dicyclohexyl carbodiimide; 1-hydroxy-7-azabenzotriazole / dimethylformamide / 12 h / 20 °C 2: 74 percent / Dowex(R) 50W H(1+) form / methanol / 2 h / 50 °C View Scheme
Multi-step reaction with 2 steps 1: 38 percent / 1,3-dicyclohexylcarbodiimide, 1-hydroxybenzo-7-azatriazole / tetrahydrofuran; dimethylformamide / Ambient temperature 2: 73 percent / Dowex 50W, MeOH / 50 °C View Scheme
Multi-step reaction with 2 steps 1: tetrahydrofuran; dimethylformamide / 36 h / Ambient temperature 2: 65 percent / 1 N HCl / methanol / 5 h / 50 °C View Scheme

6-Methyluracil (626-48-2) + ZnCl2 → sparsomycin (1404-64-4)

Conditions

Yield

Multi-step reaction with 7 steps 1: 77 percent / aq. NaOH / H2O / 40 h / 25 °C 2: 60 percent / ceric ammonium nitrate / H2O / 25 °C 3: 75 percent / dimethylsulfoxide / 50 h / 25 °C 4: 90 percent / 3 N aq. NaOH / methanol; dioxane / 24 h / 25 °C 5: 1.) triethylamine / 1.) DMF, THF, 0 deg C, 5 min, 2.) RT, 4 h 6: tetrahydrofuran; dimethylformamide / 36 h / Ambient temperature 7: 65 percent / 1 N HCl / methanol / 5 h / 50 °C View Scheme

5-hydroxymethyl-6-methyluracil (147-61-5) → sparsomycin (1404-64-4)

Conditions	Yield
Multi-step reaction with 6 steps 1: 60 percent / ceric ammonium nitrate / H2O / 25 °C 2: 75 percent / dimethylsulfoxide / 50 h / 25 °C 3: 90 percent / 3 N aq. NaOH / methanol; dioxane / 24 h / 25 °C 4: 1.) triethylamine / 1.) DMF, THF, 0 deg C, 5 min, 2.) RT, 4 h 5: tetrahydrofuran; dimethylformamide / 36 h / Ambient temperature 6: 65 percent / 1 N HCl / methanol / 5 h / 50 °C View Scheme
Multi-step reaction with 4 steps 1: 63 percent / K2S2O8, AgNO3 / H2O / 1.) 90-100 deg C; 2.) room temp. 16 h 2: 40 percent / dimethylformamide / 96 h / Ambient temperature 3: 90 percent / NaOH / methanol; dioxane; H2O / 16 h / 40 °C 4: 1.) Triethylamine, Ethyl chloroformate / 1.) THF/DMF, 0 deg C, 4 h; 2.) THF/DMF, room temp., 48 h View Scheme

1,2,3,4-tetrahydro-6-methyl-2,4-dioxo-5-pyrimidinecarbaldehyde (24048-74-6) → sparsomycin (1404-64-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: 75 percent / dimethylsulfoxide / 50 h / 25 °C 2: 90 percent / 3 N aq. NaOH / methanol; dioxane / 24 h / 25 °C 3: 1.) triethylamine / 1.) DMF, THF, 0 deg C, 5 min, 2.) RT, 4 h 4: tetrahydrofuran; dimethylformamide / 36 h / Ambient temperature 5: 65 percent / 1 N HCl / methanol / 5 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1: 40 percent / dimethylformamide / 96 h / Ambient temperature 2: 90 percent / NaOH / methanol; dioxane; H2O / 16 h / 40 °C 3: 1.) Triethylamine, Ethyl chloroformate / 1.) THF/DMF, 0 deg C, 4 h; 2.) THF/DMF, room temp., 48 h View Scheme

C11H12N2O6 → sparsomycin (1404-64-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrahydrofuran; dimethylformamide / 36 h / Ambient temperature 2: 65 percent / 1 N HCl / methanol / 5 h / 50 °C View Scheme

(E)-β-(2,4-Dioxo-6-methyl-1,2,3,4-tetrahydropyrimidin-5-yl)acrylic acid (28277-67-0) → sparsomycin (1404-64-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) triethylamine / 1.) DMF, THF, 0 deg C, 5 min, 2.) RT, 4 h 2: tetrahydrofuran; dimethylformamide / 36 h / Ambient temperature 3: 65 percent / 1 N HCl / methanol / 5 h / 50 °C View Scheme

Ethyl (E)-3-(2,4-Dioxo-6-methyl-5-pyrimidinyl)acrylate (28277-68-1) → sparsomycin (1404-64-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 90 percent / 3 N aq. NaOH / methanol; dioxane / 24 h / 25 °C 2: 1.) triethylamine / 1.) DMF, THF, 0 deg C, 5 min, 2.) RT, 4 h 3: tetrahydrofuran; dimethylformamide / 36 h / Ambient temperature 4: 65 percent / 1 N HCl / methanol / 5 h / 50 °C View Scheme
Multi-step reaction with 2 steps 1: 90 percent / NaOH / methanol; dioxane; H2O / 16 h / 40 °C 2: 1.) Triethylamine, Ethyl chloroformate / 1.) THF/DMF, 0 deg C, 4 h; 2.) THF/DMF, room temp., 48 h View Scheme

6-Methyluracil (626-48-2) → sparsomycin (1404-64-4)

Conditions

Yield

Multi-step reaction with 5 steps 1: 73 percent / 5percent aq NaOH / H2O / 16 h / Ambient temperature 2: 63 percent / K2S2O8, AgNO3 / H2O / 1.) 90-100 deg C; 2.) room temp. 16 h 3: 40 percent / dimethylformamide / 96 h / Ambient temperature 4: 90 percent / NaOH / methanol; dioxane; H2O / 16 h / 40 °C 5: 1.) Triethylamine, Ethyl chloroformate / 1.) THF/DMF, 0 deg C, 4 h; 2.) THF/DMF, room temp., 48 h View Scheme

sparsomycin (1404-64-4) + methyl iodide (74-88-4) → >-N-<1-(hydroxymethyl)-2-<<(methylthio)methyl>sulfinyl>ethyl>-3-(1,2,3,4-tetrahydro-1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-2-propenamide (141562-46-1)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide for 3h; Ambient temperature;	75%

sparsomycin (1404-64-4) + acetyl chloride (75-36-5) → O-acetyl-sparsomycin (91922-09-7)

Conditions	Yield
In pyridine; dichloromethane Ambient temperature;	30%

sparsomycin (1404-64-4) → isosparsomycin (58462-97-8)

Conditions	Yield
In water for 0.833333h; Irradiation;

Upstream product

• 95407-15-1 O-(methoxymethyl)sparsomycin 
• 52-90-4 L-Cysteine 
• 73-22-3 L-Tryptophan 
• 77826-38-1 S-Oxo-S<(methylthio)methyl>-D-cysteinol 
• 28277-67-0 (E)-β-(2,4-Dioxo-6-methyl-1,2,3,4-tetrahydropyrimidin-5-yl)acrylic acid 
• 95407-13-9 (R_S)-O-(methoxymethyl)-S-((methylthio)methyl)-D-cysteinol S-oxide 
• 626-48-2 6-Methyluracil 
• 147-61-5 5-hydroxymethyl-6-methyluracil 
• 24048-74-6 1,2,3,4-tetrahydro-6-methyl-2,4-dioxo-5-pyrimidinecarbaldehyde 
• 28277-68-1 Ethyl (E)-3-(2,4-Dioxo-6-methyl-5-pyrimidinyl)acrylate 

Related news

Research ArticleSynthesis of SPARSOMYCIN (cas 1404-64-4) Analogs as Potential Antitumor Agents09/09/2019

No information is available on the structural requirements for the antitumor activity of sparsomycin, an antibiotic obtained from the fermentation broth of Streptomyces sparsogenes. Its high in vivo and in vitro activity, novel structure, and uncommon mode of action have, therefore, suggested th...detailed

Potentiation of cisplatin antitumor activity on L1210 leukemia s.c. by SPARSOMYCIN (cas 1404-64-4) and three of its analogues09/05/2019

Sparsomycin (Sm) is a known antibiotic derived from Streptomyces. Its potential antitumor activity stimulated the search for a synthetic production method and the development of new derivatives. In a recent screening investigation, three Sm analogues appeared to be more active and considerably l...detailed

ORGINAL ARTICLEBiochemical studies on the production of SPARSOMYCIN (cas 1404-64-4) antibiotic by Pseudomonas aeurginosa, AZ-SH-B8 using plastic wastes as fermented substrate09/03/2019

Hundred and twenty microbial isolates could be isolated from different soil samples collected from different localities in Egypt. One of the bacterial cultures AZ-SH-B8 was found to produce a wide spectrum antimicrobial agent when cultivated on plastic wastes. The bacterial culture AZ-SH-B8 coul...detailed

DispatchRibosomal translocation: SPARSOMYCIN (cas 1404-64-4) pushes the button09/02/2019

New insights into the way that the tRNA:mRNA complex is translocated on the ribosome during protein synthesis have come from the recent observation that binding of the antibiotic sparsomycin in the peptidyl transferase center can trigger these large-scale movements.detailed

Relevant articles and documents

Synthesis and activity of pyrimidinylpropenamide antibiotics: The alkyl analogues of sparsomycin

Facile syntheses of sparsomycin (3) and its four analogues (4-7) based on diastereoselective oxidation of sulfide, sulfenylation, and coupling of 6-methyluracylacryllic acid with monooxodithioacetal amine, are described. Studies on the biological activity of morphological reversion on src ts-NRK cells were also carried out.

Biosynthesis of the antitumor antibiotic sparsomycin

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Total Synthesis of the Antibiotic Sparsomycin, a Modified Uracil Amino Acid Monoxodithioacetal

The total syntheses of sparsomycin (1), a naturally occurring antibiotic and antitumor substance, and its three stereomers 65-67 are described for the first time.In a convergent approach, the carboxylic acid 2 and the amine 3 were synthesized followed by amide formation (Scheme I).The acid 2 was prepared (23percent yield) from 6-methyluracil (12) by coupling the aldehyde 19 with the phosphorane 20 (Scheme III).The synthesis of the amine 3, especially challenging because of the monoxodithioacetal moiety, was accomplished by the reaction of a cysteine α-halo sulfoxide derivative 8 with sodium methylmercaptide (Scheme II, route B).Alternatively, oxidation of the dithioacetals 23-26 was unsatisfactory, yielding predominantly the undesired regioisomers 27B-30B (Table I).Procedures are given for the preparation and separation of the α-halo sulfoxide diastereomers 33,35, 36-41, and 52-54.By use of these procedures, the amino alcohol monoxodithioacetals 3 and 60 were prepared in five steps (40percent yield) from the D-cystine derivative 59 having the SC chirality of sparsomycin (Scheme VII).Finally, sparsomycin (1) and the SC diastereomer 67 were prepared (40percent yield) by mixed anhydride coupling of 2 with 3 and 60, respectively (Schemes I and X).In addition, syntheses of the RC enantiomer 65 and corresponding diastereomer 66 are described (Scheme IX).The CD spectra of 1 and its three stereomers are also discussed.