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项目整合的本质是一项集合成方法学、反应工程学与过程分析技术于一体的系统工程。其核心逻辑可以概括为以下几点：源头优选：利用如N-硝胺化学等底层方法学突破，从分子层面颠覆传统高成本、高污染路线。过程强化：依托连续流技术，攻克有机金属试剂应用、光化学反应放大等“不可能”任务，实现高危工艺的本质安全。系统集成：整合“反应-淬灭-分离”全流程，利用微流控与在线分析技术，消除批次间的差异，实现药品制造的连续化与智能化。当前，中间体工艺研发正在经历从“经验驱动”向“数据驱动”的转变。AI辅助路线设计、自动化高通量筛选与连续制造平台的结合，将使得“分子结构与最优工艺路径”之间的映射关系逐渐清晰。未来的竞争优势，将属于那些能够将底层化学创新与先进工程技术进行无缝整合的研发体系。
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其它产品项目整合

Bredereck's Reagent CAS Registry Number: 5815-08-7 叔丁氧基双(二甲胺基)甲烷

CAS Name: 1-(1,1-Dimethylethoxy)-N,N,N',N'-tetramethylmethanediamine
Additional Names: bis(dimethylamino)-tert-butyloxymethane; tert-butoxybis(dimethylamino)methane; tert-butoxy-N,N,N',N'-tetra...
Literature References: Aminal ester used in condensation reactions. Prepn: H. Bredereck et al., Angew. Chem. Int. Ed. 6, 356 (1967); idem et al., Ber. 101, 41 (1968). Synthetic applications: B. M. Trost, M. Preckel, J. Am. Chem. Soc. 95, 7862 (1973); W. Haefliger, H. Knecht, Tetrahedron Lett. 25, 285 (1983); J.-P. Vors, J. Heterocycl. Chem. 28, 1043 (1991); A. C. Spivey et al., J. Org. Chem. 65, 5253 (2000); E. Morera et al., Org. Lett. 4, 1139 (2002); S. Csihony et al., Adv. Synth. Catal. 346, 1081 (2004). Review: W. Kantlehner, J. Prakt. Chem. Chem.-Ztg. 337, 418-421 (1995).

Hydroxyproline CAS Registry Number: 51-35-4 L-羟脯氨酸

CAS Name: (4R)-4-Hydroxy-L-proline
Additional Names: Hyp; Ls-hydroxyproline; (-)-(2S,4R)-4-hydroxyproline; trans-4-hydroxyproline; 4(R)-hydroxy-2(S)-pyrrolidinecarboxylic acid
Percent Compos...
Literature References: Amino acid analog of proline, q.v.; non-essential for human development. Shows cis-trans isomerism. Constituent of collagen, q.v. Isoln from gelatin: E. Fischer, Ber. 35, 2660 (1902). Synthesis: H. Leuchs, Ber. 38, 1937 (1905); and structure determn: H. Leuchs, J. F. Brewster, Ber. 46, 986 (1913). Stereochemistry: Hudson, Neuberger, J. Org. Chem. 15, 24 (1950). Early chemistry and biochemistry: Amino Acids and Proteins, D. M. Greenberg, Ed. (Charles C. Thomas, Springfield, IL, 1951) 950 pp., passim; J. P. Greenstein, M. Winitz, Chemistry of the Amino Acids vols 1-3 (John Wiley and Sons, Inc., New York, 1961) pp. 2018-2042, passim. Flow sheets of four different syntheses: Chem. Eng. News 40, 40 (Nov. 12, 1962). One pot synthesis: S. G. Ramaswamy, E. Adams, J. Org. Chem. 42, 3440 (1977). Proof of occurence in plants: D. Ashford, A. Neuberger, Trends Biochem. Sci. 5, 245 (1980). Effects of cis-trans isomerism on protein structure: N. Panasik, Jr. et al., Int. J. Pept. Protein Res. 44, 262 (1994). Review: R. Kuttan, A. N. Radhakrishnan, Adv. Enzymol. 37, 273-348 (1973). Review of metabolism: E. Adams, L. Frank, Annu. Rev. Biochem. 49, 1005-1061 (1980).

Nateglinide CAS Registry Number: 105816-04-4 那格列奈

CAS Name: N-[[trans-4-(1-Methylethyl)cyclohexyl]carbonyl]-D-phenylalanine
Additional Names: (-)-N-(trans-4-isopropylcyclohexyl-1-carbonyl)-D-phenylalanineTrademarks: Fastic (Ajinomoto); Starlix...
Literature References: Amino acid derivative that stimulates insulin secretion. Prepn: S. Toyoshima et al., EP 196222; eidem, US 4816484 (1986, 1989 both to Ajinomoto); H. Shinkai et al., J. Med. Chem. 32, 1436 (1989). Effect on insulin secretion: Y. Sato et al., Diabetes Res. Clin. Pract. 12, 53 (1991). HPLC determn in plasma and urine: I. Ono et al., J. Chromatogr. B 692, 397 (1997). Series of articles on pharmacology, pharmacokinetics and toxicology: Yakuri to Chiryo 25, Suppl. 1, S9-S239 (1997). Toxicity data: K. Hasegawa et al., ibid. S5, C.A. 126, 152622 (1997).

g -Carboxyglutamic Acid CAS Registry Number: 53861-57-7 gamma-羧基-L-谷氨酸

CAS Name: 3-Amino-1,1,3-propanetricarboxylic acid
Additional Names: g-carboxy-L-glutamic acid; L-g-carboxyglutamic acid; Gla
Percent Composition: C 37.70%, H 4.75%, N 7.33%, O 50.22%
Literature References: Amino acid found in blood coagulation proteins (prothrombin, Factor VII, Factor IX, Factor X, q.q.v.), plasma proteins and proteins from calcified tissue. Presence of Gla confers metal binding properties to the protein. Discovery in prothrombin: J. Stenflo, Proc. Natl. Acad. Sci. USA 71, 2730 (1974); G. L. Nelsestuen et al., J. Biol. Chem. 249, 6347 (1974). Synthesis: S. Danishefsky et al., J. Am. Chem. Soc. 101, 4385 (1979); of DL-form: H. R. Morris et al., Biochem. Biophys. Res. Commun. 62, 856 (1975); W. Märki, R. Schwyzer, Helv. Chim. Acta 58, 1471 (1975); B. Weinstein et al., J. Org. Chem. 41, 3634 (1976). Resolution of D- and L-forms: W. Märki et al., Helv. Chim. Acta 60, 798 (1977). Biosynthesis by vitamin K-dependent carboxylation of glutamic acid: C. T. Esmon et al., J. Biol. Chem. 250, 4744 (1975). Metal binding properties: G. L. Nelsestuen et al., Biochem. Biophys. Res. Commun. 65, 233 (1975); G. L. Nelsestuen, J. Biol. Chem. 251, 5648 (1976); R. Robertson et al., ibid. 253, 5880 (1978); S. P. Bajaj et al., ibid. 257, 3726 (1982). HPLC determn in proteins, bone, urine: M. Kuwada, K. Katayama, Anal. Biochem. 117, 259 (1981). Reviews: J. Stenflo, J. W. Suttie, Annu. Rev. Biochem. 46, 157-172 (1977); R. E. Olson, J. W. Suttie, Vitam. Horm. 35, 59-108 (1977); J. W. Suttie, Crit. Rev. Biochem. 8, 191-223 (1980); J. P. Burnier et al., Mol. Cell. Biochem. 39, 191-207 (1981).

b -Carboxyaspartic Acid CAS Registry Number: 75898-26-9 2-氨基乙烷-1,1,2-三羧酸

CAS Name: 2-Amino-1,1,2-ethanetricarboxylic acid
Additional Names: Asa
Percent Composition: C 33.91%, H 3.98%, N 7.91%, O 54.20%
Literature References: Amino acid found in ribosomal proteins of E. coli; homolog of g-carboxyglutamic acid. Isoln and synthesis of DL-form: M. R. Christy et al., J. Am. Chem. Soc. 103, 3935 (1981). Synthesis of DL-form: E. B. Henson et al., Tetrahedron 37, 2561 (1981); N. E. Dixon, A. M. Sargeson, J. Am. Chem. Soc. 104, 6716 (1982). Quantitative analysis method: P. V. Hauschka et al., Anal. Biochem. 108, 57 (1980). Chemical reactivity: M. R. Christy, T. H. Koch, J. Am. Chem. Soc. 104, 1771 (1982). Crystal structure and pKa values of DL-zwitterion: B. Richey et al., Biochemistry 21, 4819 (1982). Asymmetric synthesis of D-form: R. M. Williams et al., J. Am. Chem. Soc. 110, 482 (1988). Review: T. H. Koch et al., Methods Enzymol. 107, 563-575 (1984).

Fotemustine CAS Registry Number: 92118-27-9 福莫司汀

CAS Name: [1-[[[(2-Chloroethyl)nitrosoamino]carbonyl]amino]ethyl]phosphonic acid diethyl ester
Additional Names: (±)-diethyl [1-[3-(2-chloroethyl)-3-nitrosoureido]ethyl]phosphonate; 1-[N-(...
Literature References: Amino acid-linked nitrosourea alkylating agent. Prepn: G. Lavielle, C. Cudennec, FR 2536075; eidem, US 4567169 (1984, 1986 both to ADIR). Clinical evaluation in advanced cancers: D. Khayat et al., Cancer Res. 47, 6782 (1987); in disseminated malignant melanoma: D. Khayat et al., J. Natl. Cancer Inst. 80, 1407 (1988).

D -Galactosamine CAS Registry Number: 7535-00-4 半乳糖胺

CAS Name: 2-Amino-2-deoxy-D-galactose
Additional Names: chondrosamine; GalN
Percent Composition: C 40.22%, H 7.31%, N 7.82%, O 44.65%
Literature References: Amino sugar isolated from chondroitin sulfate, q.v.: P. A. Levene, F. B. La Forge, J. Biol. Chem. 18, 123 (1914). Sepn of a- and b-anomers: P. A. Levene, ibid. 57, 337 (1923). Synthesis: S. P. James et al., Nature 156, 308 (1945) eidem, J. Chem. Soc. 1946, 625; R. Kuhn, W. Kirschenlohr, Ann. 600, 126 (1956); P. A. Gent et al., J. Chem. Soc. Perkin Trans. 1 1972, 277. Chemistry: D. Horton in The Amino Sugars Vol. 1A, R. W. Jeanloz, Ed. (Academic, New York, 1969) pp 133-145. Inducer of exptl hepatitis: D. Keppler et al., Exp. Mol. Pathol. 9, 279 (1968); K. Decker, D. Keppler in Progress in Liver Diseases Vol. IV, H. Popper, F. Schaffner, Eds. (Grune Stratton, New York, 1972) p 183. Powerful inhibitor of hepatic RNA synthesis: D. Keppler et al., J. Biol. Chem. 249, 211 (1974); T. Anukarahanonta et al., Eur. J. Cancer 16, 1171 (1980).

Miglustat CAS Registry Number: 72599-27-0 麦格司他

CAS Name: (2R,3R,4R,5S)-1-Butyl-2-(hydroxymethyl)-3,4,5-piperidinetriol
Additional Names: N-butyldeoxynojirimycin; N-butylmoranolineTrademarks: Zavesca (Actelion)
Percent Composition: C 54.7...
Literature References: Amino sugar; inhibitor of glucosyltransferase, an enzyme involved in the biosynthesis of glycosphingolipids. Prepn: B. Junge et al., DE 2758025; see also, eidem, US 4639436 (1979, 1987 both to Bayer). Improved synthesis: E. W. Baxter, A. B. Reitz, J. Org. Chem. 59, 3175 (1994); C. R. R. Matos et al., Synthesis 1999, 571. In vitro efficacy vs HIV: A. Karpas et al., Proc. Natl. Acad. Sci. USA 85, 9229 (1988). Inhibition of glycolipid biosynthesis: F. M. Platt et al., J. Biol. Chem. 269, 8362 (1994). Clinical evaluation in Gaucher's disease: T. Cox et al., Lancet 355, 1481 (2000). Review of pharmacology and clinical development in Gaucher's disease: P. L. McCormack, K. L. Goa, Drugs 63, 2427-2434 (2003).

Ribostamycin CAS Registry Number: 25546-65-0 核糖霉素

CAS Name: O-2,6-Diamino-2,6-dideoxy-a-D-glucopyranosyl-(1®4)-O-[b-D-ribofuranosyl-(1®5)]-2-deoxy-D-streptaminePercent Composition: C 44.93%, H 7.54%, N 12.33%, O 35.20%
Literature References: Aminocyclitol antibiotic belonging to the neomycin, q.v., group of antibiotics. Produced by Streptomyces ribosidificus (formerly called S. thermoflavus). Taxonomy, isoln and toxicity data: T. Shomura et al., J. Antibiot. 23, 155 (1970). Prepn: eidem, DE 1814735 corresp to US 3661892, US 3799842 (1969, 1972, 1974 all to Meiji). Structure: E. Akita et al., J. Antibiot. 23, 173 (1970). Synthesis from neamine, q.v.: Ito et al., Antimicrob. Agents Chemother. 1970, 33; eidem, Agric. Biol. Chem. 34, 980 (1970); V. Kumar, W. A. Remers, J. Org. Chem. 43, 3327 (1978); 46, 4298 (1981). Total synthesis: H. Fukami et al., Tetrahedron Lett. 1976, 545; eidem, Agric. Biol. Chem. 41, 1689 (1977). In vitro antibacterial activity: E. Yourassowsky, M. P. Vander Linden, Arzneim.-Forsch. 26, 184 (1976).

Tobramycin CAS Registry Number: 32986-56-4 妥布霉素

CAS Name: O-3-Amino-3-deoxy-a-D-glucopyranosyl-(1®6)-O-[2,6-diamino-2,3,6-trideoxy-a-D-ribo-hexopyranosyl-(1®4)]-2-deoxy-D-streptamine
Additional Names: 4-[2,6-diamino-2,3,6-trideoxy-a-D-glycop...
Literature References: Aminoglycoside antibiotic; component of the nebramycin complex produced by Streptomyces tenebrarius. See also apramycin. Series of articles on isolation, separation and evaluation of the nebramycin complex: Antimicrob. Agents Chemother. 1967, 314-348. Elucidation of structure: K. F. Koch, J. A. Rhoades, Antimicrob. Agents Chemother. 1970, 309. Synthesis: Y. Takagi et al., Bull. Chem. Soc. Jpn. 49, 3649 (1976); M. Tanabe et al., Tetrahedron Lett. 1977, 3607. Toxicology: J. S. Welles et al., Toxicol. Appl. Pharmacol. 22, 332 (1972). Comprehensive description: A. K. Dash, Anal. Profiles Drug Subs. Excip. 24, 579-613 (1996). Clinical trial in cystic fibrosis patients: B. W. Ramsey et al., N. Engl. J. Med. 340, 23 (1999). Review of clinical experience: H. Lode, Curr. Ther. Res. 59, 420-453 (1998).