I will assume you are using the Persian "Sikander" (also spelled Sekandar), better known as Alexander the Great of Macedon. It has come down through history that he developed an illness while in Babylon and died from it. The Shahnameh, an epic Persian poem written c. 1000 CE by Abolqasem Ferdowsi, simply says, "...he fell sick, and he knew that his end was approaching."
The New England Journal of Medicine claimed to have cracked the case in 1998, saying it was probably typhoid fever. It will never be known for sure as there are no reliable medical records from 323 BCE and has been the source of much discussion, usually involving poison.
As for Alexander failing in his ambition, I will assume that you mean the conquest of India. His first ambition was to do what his father failed at, defeating Persia. He was successful at that, and followed up that triumph with the conquest of Egypt. By the time he reached India, his men had marched a long way and fought for five years. After Alexander defeated Porus and his elephants he realized that India was larger than he had thought and his men begged him to let them go home. It was on his way back to Macedon when he died.