Confirming the stereochemistry by synthesis

The other two chiral centres at the right-hand end of the chain are so far removed from the ring (by 10 CH₂ groups) that there is no simple way to determine their stereochemistry relative to the three at the left-hand end by NMR. The solution to problems of assignment like this is often to make the various isomers by unambiguous synthesis and compare the NMR spectra of the natural and synthetic compounds. This is what Mori did in this case. The chiral pool can again be called into play by using another amino acid, L-isoleucine, as starting material. First the amino group must be converted to a leaving group by diazotization with nitrous acid (sodium nitrite in dilute HCl) and substituted by water to give a hydroxy acid. The acid is esterified and reduced to a diol.

Conversion of the diol’s primary hydroxyl group to a leaving group (here a tosylate) allows the epoxide to be formed with retention of the two stereogenic centres of the starting mate rial. Cyclization in base gives an epoxide. Overall, the enantiomerically pure starting mate rial is converted stereospecifically into a single enantiomer of a single diastereoisomer of the epoxide.

Before we go on, look back at the fi rst reaction of this sequence—the conversion of L-leucine to the hydroxy acid. The stereochemistry may surprise you: look carefully and you will see that the amino group has been displaced with retention of stereochemistry. Retentive substitutions usually indicate double inversions, and here the carboxylic acid gets involved in the displacement to give (with inversion) a very unstable compound called an α-lactone whose strained ring is opened by water, also with inversion.

The epoxide may now be opened with a nucleophile to give the right-hand half of the target molecule. The alkyne shown below, which has an anti-relationship between the hydoxyl and methyl groups, was made and linked to the left-hand half of penaresidin A by using it to attack the aldehyde the method described above. However, the final product was not the same as natural penarisidin A!

Clearly, some aspect of relative stereochemistry was wrong. So the synthesis was repeated, this time using the syn diastereosiomer of the substituted alkyne obtained using one of the methods. With this isomer the final compound had spectroscopic data identical with the natural product, and the question of its stereochemistry was solved. It is not uncommon for synthesis to be the only reliable way of proving the detailed structure of a compound.

اخر الاخبار

اخبار العتبة العباسية المقدسة

بيان لمكتب المرجعية العليا حول نشر صور السيد السيستاني في الأماكن العامة

متحف الكفيل: إنجاز المرحلة الرابعة من مشروع متحف العتبة العسكرية المقدسة

تضمن عرضًا مسرحيًّا.. شعبةُ الخطابة النسويّة تقيم مجلس عزاء بذكرى شهادة الإمام الحسن (عليه السّلام)

الأمين العام للعتبة العبّاسية المقدّسة يتفقد مجموعة مواكب أمّ البنين (عليها السلام) لخدمة الزائرين

المزيد

الآخبار الصحية

تسارع الشيخوخة.. متى يبدأ وأي الأعضاء أكثر تأثرا؟

9 مسببات شائعة للالتهاب المزمن قد تهدد صحتك

باحثون يطورون علاجا لهشاشة العظام.. النتائج مذهلة

تحمي من أمراض عديدة.. 6 فوائد لتناول البطاطا الحلوة

المزيد

الآخبار التكنلوجية

عودة التعاون الفضائي بين روسيا وأميركا.. وبحث ملفات "هامة"

المعلمون في خطر.. خاصية جديدة في "تشات جي بي تي" تشرح الدروس

بشرى لمرضى الشلل.. شريحة في الدماغ قد تتيح التحكم بالأدوات

مدينة غارقة.. هل يخفي قاع البحر الكاريبي سرّ حضارة مفقودة؟

المزيد

مواضيع ذات صلة

The Hammett relationship

Systematic structural variation

Crossover experiments

Labelling experiments reveal the fate of individual atoms

Be sure of the structure of the product

Variation in the structure of the aldehyde

formation of an ester intermediate

formation of an intermediate dimeric adduct

Be sure of the structure of the product

Variation in the structure of the aldehyde

Proposed mechanism C: formation of an ester intermediate

Proposed mechanism B: formation of an intermediate dimeric adduct