Oseltamivir is the active ingredient in an antiviral drug (Tamiflu®) used for the prevention and tre — Physical Chemistry Chemistry Question
Synthesis of oseltamivir
Oseltamivir is the active ingredient in an antiviral drug (Tamiflu®) used for the prevention and treatment of influenza A and B. There are several ways to synthesize oseltamivir.
Determine the number of stereoisomers of shikimic acid (which possesses three independent stereogenic centers and no particular symmetry).
Model Answer
Three independent stereogenic centers (no particular symmetry) so 2^3 = 8 stereoisomers.
Explain the meaning of the '-' sign in (-)-shikimic acid.
Model Answer
Correct statements: It is the sign of the specific rotatory power of shikimic acid. Shikimic acid is levorotatory. Shikimic acid rotates the polarization plane to the left when the observer faces the source.
Give the structure of A.
Draw the structure of a chlorinated compound involved as a reaction intermediate in the formation of A.
The 1H NMR spectrum of compound A is partly described below (the OH signals have not been reported). The two hydrogen atoms linked to C6 are diastereotopic and appear as two different signals. A (δ, ppm in CDCl3, 400 MHz): 6.78 (1H, m), 4.37 (1H, m), 4.20 (2H, q, 7.3), 4.00 (1H, dt, 7.2 and 5.2), 3.69 (1H, dd, 7.2 and 4.0), 2.70 (1H, dd, 18.4 and 5.2), 2.21 (1H, dd, 18.4 and 5.2), 1.28 (3H, t, 7.3). Assign all the 1H NMR signals to the corresponding hydrogen atom(s) of A. [VISUAL]
Data about compound X:
- Mass composition: %C = 70; %H = 12; %O = 18
- 1H NMR (δ, ppm in CDCl3, 300 MHz): 2.42 (q, 2H), 1.05 (t, 3H)
- Partial IR spectroscopic data: intense absorption at 1715 cm-1
Identify X, draw its structure and draw the structure of B.
Draw the structure of a hemiacetal involved as a reaction intermediate in the formation of B.
Identify the chemical role(s) of the steps involved in converting shikimic acid to B.
Model Answer
Correct statements: Protect the C3 and C4 hydroxy groups; Prepare the derivatization of the C3 hydroxy group; Differentiate chemically the 3 hydroxy groups
The intermediate sulfonate D (C15H26O7S) has a vibration band around 3300 cm–1. The by-product D’ is an isomer of D. It also has a vibration band around 3300 cm–1 but does not lead to an epoxide under the proposed conditions. D” is not an isomer of D but has also a vibration band around 3300 cm–1. Unlike D’, it can undergo epoxidation under the proposed conditions. The product then obtained, E”, has also a vibration band around 3300 cm–1.
Draw E with the stereochemistry of all stereochemical centers.
Using the given information and a retrosynthetic analysis, draw the structures of D, D’, D”, and E” (including their stereochemistry).
Draw F with the stereochemistry of all stereochemical centers.
Give the stereochemical descriptors of the stereogenic centers of oseltamivir.