- An efficient route for the preparation of a 21-fluoro progestin-16 alpha,17 alpha-dioxolane, a high-affinity ligand for PET imaging of the progesterone receptor.
-
Two different synthetic routes were explored for the synthesis of fluoro furanyl norprogesterone (FFNP) 1, a high-affinity ligand for the progesterone receptor (PgR) that is being developed as a PET imaging agent for PgR-positive breast cancer. Both approaches proceed through a key intermediate, triol 5. The first approach, starting from keto-ketal 2, employed a dioxenyl group as a synthon for installing a corticosteroid side chain in keto-alcohol 4. The second approach, starting from propargylic acetate 12b, involved the application of a two-step method, a Pd(II)-catalyzed oxidative rearrangement followed by a base-catalyzed acetate rearrangement of the intermediate unsaturated acetate 13b, to generate the requisite corticosteroid side chain in keto-acetate 14b. This intermediate was further elaborated to the final product 1 via efficient dihydroxylation with potassium permangnate, furan acetalization with scandium triflate, and mesylation and fluorination reactions. The palladium-catalyzed route is considerably more efficient than the dioxene approach for the synthesis of key intermediate triol 5, and the scandium triflate-catalyzed acetalization, in particular, led to a considerable improvement in the overall yield of the endo furan acetal alcohol 16a. This route provides a major improvement in the overall yield of the final progestin target, FFNP 1.
- Vijaykumar, Dange,Mao, Wang,Kirschbaum, Karen S,Katzenellenbogen, John A
-
-
Read Online
- Bromine- and iodine-substituted 16α,17α-dioxolane progestins for breast tumor imaging and radiotherapy: Synthesis and receptor binding affinity
-
Progesterone receptors (PRs) are present in many breast tumors, and their levels are increased by certain endocrine therapies. We describe the synthesis and PR binding affinities of a series of bromine- and iodine-substituted 16α,17α-dioxolane progestins, some of which, when appropriately radiolabeled, are potential agents for diagnostic imaging of PR-positive breast tumors using positron emission tomography (PET) and for radiotherapy. These compounds were synthesized from halogenated furanyl, phenyl, and thiophenyl aldehydes and a progestin 16α,17α,21-triol (5) in the presence of HClO4 or Sc(OTf)3 in high yields under optimized conditions. A new reagent, perfluoro-1-butanesulfonyl fluoride (PBSF), was used to convert the C-21 OH to F in high yields. The relative binding affinities (RBAs) of the most promising compounds for the PR (RBA of R5020 = 100) were 16α,17α-[(R)-1′-α-(5-bromofurylmethylidene)dioxyl] -21-hydroxy-19-norpregn-4-ene-3,20-dione (endo-6; RBA = 65 and moderate lipophilicity), 21-fluoro-16α,17α-[(R)-1′-α-(5- iodofurylmethylidene)dioxyl]-19-norpregn-4-ene-3,20-dione (endo-14; RBA = 40) and 21-fluoro-16α,17α-[(S)-1′-β-(-iodophenylmethylidene) dioxyl]-19-norpregn-4-cne-3,20-dione (exo-16; RBA = 34).
- Zhou, Dong,Carlson, Kathryn E.,Katzenellenbogen, John A.,Welch, Michael J.
-
-
Read Online
- Preparation method of norethindrone acetate (by machine translation)
-
The invention discloses a preparation method of norethindrone acetate and belongs to the technical field of drug preparation and processing. The method uses 19 - demethyl -4 - androstenedione as a starting raw material, protects, acetylenically, hydrolyses and esterifies 4 steps to prepare the norethindrone acetate. To the preparation method of the norethindrone acetate, the defects of a traditional process are overcome, reaction conditions are mild, impurities are reduced, overall conversion rate is high, operation is simple and convenient, and the method is suitable for industrial production and has a wide market prospect. (by machine translation)
- -
-
Paragraph 0008; 0034; 0038
(2020/11/23)
-
- PROCESS FOR THE PURIFICATION OF NORETHINDRONE AND NORETHINDRONE ACETATE
-
The present invention provides a process for the purification of norethindrone (I) from a mixture of dimethylformamide (DMF) and water. The invention further provides two processes for the purification of norethindrone acetate (II) from a mixture of dichloromethane:n-heptane (Process A) and from a mixture of ethanol:water (Process B).
- -
-
Page/Page column 4
(2014/10/18)
-
- Using benzotriazole esters as a strategy in the esterification of tertiary alcohols
-
Benzotriazole esters formed in situ were found to be efficient intermediates in the esterification of tertiary alcohols using 4-(dimethylamino)pyridine (DMAP) as the base. These mild and basic reaction conditions allow the conversion of various substrates into esters in good yield
- Morales-Serna, Jose Antonio,Vera, Aline,Paleo, Ehecatl,Garcia-Rios, Erendira,Gavino, Ruben,Garcia De La Mora, Gustavo,Cardenas, Jorge
-
experimental part
p. 4261 - 4267
(2011/02/25)
-
- ESTERIFICATION OF ACID CHLORIDES WITH THALLIUM AND POTASSIUM SALTS OF 19-NORETHISTERONE: FORMATION OF 17-ENOL ESTERS
-
During the esterification of acid chlorides with thallium and potassium salts of 19-norethisterone, 17-enol esters were isolated.The enol esters are formed via the intermediate, 4-estrene-3,17-dione.
- Herz, Josef E.,Gunatilaka, A. A. Leslie,Sotheeswaran, Subramaniam,Torres, J. V.
-
p. 261 - 266
(2007/10/02)
-
- Synthesis of gon-4-enes
-
1. A therapeutic composition having progestational activity comprising as active ingredient a 17-aliphatic carboxylic acid ester of 17α-ethynyl-18-methyl-19-nortestosterone and a pharmaceutical carrier for said compound.
- -
-
-
- Synthesis of 13-alkyl-gon-4-ones
-
The preparation of 13-methylgon-4-enes and novel 13-polycarbonalkylgon-4-enes by a new total synthesis is described. 13-Alkylgon-4-enes having progestational, anabolic and androgenic activities are prepared by forming a tetracylic gonane structure unsaturated in the 1,3,5(10),9(11) and 14-positions, selectively reducing in the B- and C-rings, and converting the aromatic A-ring compounds so-produced to gon-4-enes by Birch reduction and hydrolysis.
- -
-
-
- Mono-acylation of 17-hydroxy-3-alkoxygona-2,5-(10)dienes
-
An efficient, one-step process for preparing 13-alkyl-17α alkyl, alkenyl, or alkynyl-17β-acyloxy-4-en-3-one steroids from their corresponding 13-alkyl-17α-substituted-3-alkoxygona-2,5(10)-dien-17β-ols is disclosed. Products of the instant process possess, for example, progestational activity.
- -
-
-
- 17α-Ethinyl-18-methyl-19-nortestosterone esters
-
A therapeutic compound for inhibiting ovulation comprising a 17-ester of 17α-ethinyl-18-methyl-19-nortestosterone wherein the said 17-ester group is formed from an aliphatic carboxylic acid having from six to 11 carbon atoms in the ester residue..Iaddend.
- -
-
-
