61903-30-8

Basic information

• Product Name: (R,S)-4-Hydroxy Cyclophosphamide
• Synonyms: (2R,4S)-rel-2-[Bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorin-4-ol 2-Oxide;(R,S)-4-Hydroxy Cyclophosphamide;(R,S)-4-Hydroxy Cyclophosphamide Discontinued See: H926301;(R,S)-4-Hydroxy Cyclophosphamide Kit ;(R,S)-4-Hydroxy Cyclophosphamide See: H926301;(R,S)-4-Hydroxy Cyclophosphamide, Preparation Kit
• CAS NO: 61903-30-8
• Molecular Formula: C₇H₁₅Cl₂N₂O₃P
• Molecular Weight: 277.086
• Product Categories: Chiral Reagents;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Phosphorylating and Phosphitylating Agents;Chiral Reagents, Metabolites & Impurities, Pharmaceuticals, Intermediates & Fine Chemicals, Phosphorylating and Phosphitylating Agents
• Mol File: 61903-30-8.mol
• Article Data: 6

Chemical Properties

• Appearance: /
• Storage Temp.: Hygroscopic, -86°C Freezer, Under Inert Atmosphere
• Solubility: Water
• Stability: This solution is stable for one day at room temperature
• CAS DataBase Reference: (R,S)-4-Hydroxy Cyclophosphamide(CAS DataBase Reference)
• NIST Chemistry Reference: (R,S)-4-Hydroxy Cyclophosphamide(61903-30-8)
• EPA Substance Registry System: (R,S)-4-Hydroxy Cyclophosphamide(61903-30-8)

Safety Data

• Hazardous Substances Data: 61903-30-8(Hazardous Substances Data)

Usage

Description

(R,S)-4-Hydroxy Cyclophosphamide, a metabolite of Cyclophosphamide, is a low melting off-white to pale yellow solid with significant chemical properties. It is derived from the precursor 4-hydroperoxycyclophosphamide and a reducing agent, which, when combined, form a solution with a half-life of approximately 200 minutes at room temperature.

Uses

Used in Pharmaceutical Industry:
(R,S)-4-Hydroxy Cyclophosphamide is used as an intermediate in the synthesis of various pharmaceutical compounds for its role in the metabolism of Cyclophosphamide. It plays a crucial part in the development of drugs that target specific diseases and conditions.
Used in Cancer Treatment:
(R,S)-4-Hydroxy Cyclophosphamide is used as a therapeutic agent in cancer treatment, particularly for its role in the metabolism of Cyclophosphamide, which is a widely used alkylating agent in chemotherapy. It contributes to the effectiveness of cancer treatment by aiding in the conversion of Cyclophosphamide into its active form, thereby enhancing the drug's cytotoxic properties and targeting cancer cells.
Used in Research and Development:
(R,S)-4-Hydroxy Cyclophosphamide is used as a research compound for studying the mechanisms of action, metabolism, and potential applications of Cyclophosphamide and its derivatives in various biological and medical research settings. This helps in understanding the drug's behavior and optimizing its use in clinical practice.
Used in Drug Synthesis:
(R,S)-4-Hydroxy Cyclophosphamide is used as a key component in the synthesis of new drug candidates, leveraging its properties to create novel therapeutic agents with improved efficacy, safety, and pharmacokinetic profiles. This contributes to the advancement of drug development and innovation in the pharmaceutical industry.

Upstream product

• 61903-29-5 cis-4-hydroxycyclophosphamide 
• 88685-78-3 aldophosphamide hydrate 
• 84210-72-0 cis-Mosfosfamide 
• 39800-16-3 trans-4-hydroperoxycyclophosphamide 
• 35144-64-0 aldophosphamide 
• 39800-29-8 O-3-buten-1-yl N,N-bis(2-chloroethyl)phosphorodiamidate 
• 56922-83-9 cis-4-Hydroperoxycyclophosphamide 
• 40277-05-2 trans-4-hydroxycyclophosphamide 

Downstream Products

• 35144-64-0 aldophosphamide 
• 88685-78-3 aldophosphamide hydrate 
• 61903-30-8 trans-4-hydroxycyclophosphamide 
• 40277-05-2 trans-4-hydroxycyclophosphamide 
• 61903-29-5 cis-4-hydroxycyclophosphamide 
• 343967-21-5 aldophosphamide O-methyloxime 
• 82084-80-8 (E)-aldophosphamide O-methyl oxime 
• 39800-16-3 trans-4-hydroperoxycyclophosphamide 
• 105639-84-7 C₉H₂₁Cl₂N₂O₆PS₂ 
• 84210-72-0 cis-Mosfosfamide 
• 92745-18-1 2-{(2S,4S)-2-[Bis-(2-chloro-ethyl)-amino]-2-oxo-2λ⁵-[1,3,2]oxazaphosphinan-4-ylsulfanyl}-ethanesulfonic acid 

Relevant articles and documents

Effects of N-substitution of the activation mechanisms of 4-hydroxycyclophosphamide analogues

The activation mechanisms of the N-substituted 4-hydroxycyclophosphamide analogues 4-hydroxyifosfamide (2b), 4-hydroxytrofosfamide (2c), and 3-methyl-4-hydroxycyclophosphamide (2d) were compared with that of the unsubstituted parent compound 2a. The reaction kinetics of cis-2b, -2c, and -2d are qualitatively similar to those of 2a in that they undergo ring opening to the respective aldophosphamide intermediates 3, which can reclose to the cis- or trans-4-hydroxy isomers or undergo base-catalyzed β-elimination to generate the corresponding phosphoramide mustard products 4. In contrast to the general acid catalysis observed for ring opening of 2a and 2d, the N-(chloroethyl)-substituted analogues 2b and 2c undergo specific base-catalyzed ring opening. This mechanistic difference was also illustrated by the rapid action of 2a and 2d with sodium 2-mercaptoethanesulfonate (Mesna) under acidic conditions to give the 4-(alkylthio)-substituted cyclophosphamide derivatives 5a and 5d. Compounds 2b and 2c did not react with Mesna to generate 5b and 5c under these conditions. Both the fraction of aldehyde/hydrate present at equilibrium and the cytotoxicity against L1210 cells in vitro decreased in the order 2c > 2b > 2a > 2d. The plasma-catalyzed acceleration of phosphoramide mustard generation previously reported for 2a was also observed for these analogues.

Activation Mechanisms of Mafosfamide and the Role of Thiols in Cyclophosphamide Metabolism

cis-Mafosfamide (cis-5) (ASTA Z7557), a stable analogue of cis-4-hydroxycyclophosphamide (cis-2), undergoes rapid decomposition in aqueous phosphate buffer or plasma at pH 7.4 and 37 deg C.The reaction kinetics of cis-5 are complex, and trans-mafosfamide (trans-5) and cis-2 are produced and subsequently disappear over the course of the reaction.The rates of decomposition of cis-5 as well as cis-2 were much faster in plasma than in buffer.The cis-trans isomerization of cis-5 occured by a specific-base-catalyzed process via iminocyclophosphamide (8) as a transient intermediate.In contrast, formation of cis- and trans-mafosfamide (5) from cis-2 and MESNA (sodium 2-mercaptoethanesulfonate) proceeded by an acid-catalyzed process via the hemithioacetal intermediate (6).The significance of these findings with respect to cyclophosphamide metabolism is discussed.

In situ preparation and fate of cis-4-hydroxycyclophosphamide and aldophosphamide: 1H and 31P NMR evidence for equilibration of cis- and trans-4-hydroxycyclophosphamide with aldophosphamide and its hydrate in aqueous solution

cis-4-Hydroxycyclophosphamide (2) and aldophosphamide (4) were generated in aqueous phosphate or cacodylate buffer by dimethyl sulfide reduction of cis-4-hydroperoxycyclophosphamide and by sodium periodate cleavage of 3,4-dihydroxybutyl N,N-bis(2-chloroethyl)phosphorodiamate, respectively; the reactions of 2 and 4 were examined by 1H and 31P NMR. Within 30-60 min (pH or pD 7.0, 25 °C) the same pseudoequilibrium mixture was established in both reactions, with cis- and trans-4-hydroxycyclophosphamide (2 and 3), aldophosphamide (4), and its hydrate (5) present in the approximate ratio of 4:2:0.3:1. Structures of the intermediates were assigned unambiguously based upon analysis of the chemical shifts and coupling constants in the proton spectra determined in D2O buffers, and the 31P assignments followed by correlation of component ratios at equilibrium. Free energy differences of 0.4, 0.4, and 0.7 kcal/mol at 25 °C were estimated between 2, 3, 5, and 4, respectively, with 2 being the most stable. The aldehyde 4 reacted most rapidly with water to give hydrate 5; cyclization of 4 to 3 occurred faster than to 2. Compound 5 is formed much faster than 3 from the diol cleavage, but 5 and 3 are produced at comparable rates from 2, suggesting that conversion of 2 to 3 can proceed by a mechanism other than ring opening. The rate of equilibration appears to be independent of buffer structure, indicating that bifunctional catalysis is not important in the ring-opening reaction. β-Elimination from 4 is rate limiting for the production of acrolein, and the rate for phosphate is 2- to 3-fold faster than for cacodylate under identical conditions. These results provide the first definitive evidence for the stability of the elusive aldehyde 4 in aqueous solution and for the existence of a preequilibrium among 2-5 prior to rate-limiting expulsion of phosphoramide mustard from 4.