Synthesis 2
Norethisterone is made from estr-4-ene-3,17-dione (bolandione), which in turn is synthesized by partial reduction of the aromatic region of the 3-O-methyl ether of estrone with lithium in liquid ammonia, and simultaneously of the keto group at C17α to a hydroxyl group, which is then oxidized back to a keto group by chromium trioxide in acetic acid. The conjugated  C4-C5 olefin and the carbonyl group at C3 is then transformed to dienol ethyl ether using ethyl orthoformate. The obtained product is ethynylated by acetylene in the presence of potassium tert-butoxide. After hydrochloride hydrolysis of the formed O-potassium derivative, during which the enol ether is also hydrolyzed, and the remaining double bond is shifted, the desired norethisterone is obtained. History
Norethisterone was synthesized for the first time by chemists Luis Miramontes, Carl Djerassi, and George Rosenkranz at Syntex in Mexico City in 1951. It was derived from ethisterone, and was found to possess about 20-fold greater potency as a progestogen in comparison. Norethisterone was the first highly active oral progestogen to be synthesized, and was preceded (as a progestogen) by progesterone (1934), ethisterone (1938), 19-norprogesterone (1944), and 17α-methylprogesterone (1949) as well as by nandrolone (1950), whereas noretynodrel (1952) and norethandrolone (1953) followed the synthesis of norethisterone. The drug was introduced as Norlutin in the United States in 1957. Norethisterone was subsequently combined with mestranol and marketed as Ortho-Novum in the United States in 1963. It was the second progestin, after noretynodrel in 1960, to be used in an oral contraceptive.
Intrauterine hypoxia (also known as fetal hypoxia) occurs when the fetus is deprived of an adequate supply of oxygen. It may be due to a variety of reasons such as prolapse or occlusion of the umbilical cord, placental infarction, maternal diabetes (prepregnancy or gestational diabetes) and maternal smoking. Intrauterine growth restriction may cause or be the result of hypoxia. Intrauterine hypoxia can cause cellular damage that occurs within the central nervous system (the brain and spinal cord). This results in an increased mortality rate, including an increased risk of sudden infant death syndrome (SIDS). Oxygen deprivation in the fetus and neonate have been implicated as either a primary or as a contributing risk factor in numerous neurological and neuropsychiatric disorders such as epilepsy, attention deficit hyperactivity disorder, eating disorders and cerebral palsy. Presentation
Maternal Consequences
Complications arising from intrauterine hypoxia are some of the leading causes of preeclampsia. Preeclampsia is a hypertensive disorder that occurs during the second trimester (after the 20th week of pregnancy) resulting from a poorly perfused placenta. Studies from the World Health Organization show that globally, about 14% (50,000- 750000 women) of maternal deaths annually are caused by preeclampsia and eclampsia.During pregnancy, women with preeclampsia faces serious risk of damage to vital organs such as the kidneys, liver, brain, and the blood system. This hypertensive disorder may also cause damage to the placenta leading to issues such as premature births, miscarriages, placental abruption, or even stillbirths. In some cases, preeclampsia can eventually lead to stroke and organ failure.